Oral Health

Oral Health

1 Overview

Summary and Quick Facts

  • Oral health problems like cavities and gum disease are very common. You may not realize that poor oral health is linked to other health problems like heart disease, diabetes and cancer.
  • This protocol will teach you about the different kinds of oral health problems and their causes. You will also learn how keeping your mouth healthy can help keep your entire body healthy.
  • Supplementation with a specialized oral probiotic has been shown to improve several measures of oral health, in clinical trials.

Oral health disorders, including cavities and periodontal disease, are among the most common health problems in US adults. Periodontal disease includes gingivitis (inflammation of the gums) and periodontitis, which can eventually lead to tooth loss. Over 20% of people 65 and older have untreated tooth decay, and approximately half of US adults aged 30 and older have periodontitis.

Omega-3 fatty acids, coenzyme Q10 and probiotics can support oral health and combat bad bacteria and inflammation in the mouth.

Oral Health and Systemic Diseases

Advanced periodontal disease is linked to both an increased risk of death and many chronic diseases, including:

  • Cardiovascular disease
  • Type 2 diabetes
  • Cognitive decline and Alzheimer’s disease
  • Cancer

Causes and Risk Factors

  • Dysbiosis in the mouth (ie, an imbalance of good and bad bacteria in the mouth) is thought to be an important cause of periodontal disease
  • Risk factors for periodontal disease include smoking, older age (especially 65 or older), and female gender

Signs and Symptoms

  • Hot and cold sensitivity and tooth pain may signal the presence of a cavity
  • Gum redness, swelling, sensitivity, and bleeding during brushing and flossing may occur in periodontal disease. There may also be gum recession, deepening pockets between teeth and gums, and bleeding on probing.

Diagnosis

A dental exam, X-rays, and a periodontal probe to measure pocket depth are used to diagnose cavities and periodontal disease

Conventional Treatment

  • Cavities are removed and replaced with a filling. A root canal may be performed in an attempt to save the tooth.
  • Gingivitis can frequently be managed with home dental hygiene and regular cleanings
  • Periodontitis treatment can involve several strategies, including:
    • Scaling and root planning
    • Antibiotics
    • Surgery

Novel and Emerging Strategies

  • Using remineralization techniques in mild cavities
  • Measuring biomolecules and bacterial and human DNA in the saliva to gauge inflammation and genetic susceptibility to periodontal disease
  • Using lasers, photodynamic therapy, or topical metformin to improve efficacy of traditional periodontal treatments

Diet and Lifestyle Considerations

Along with regular brushing and flossing:

  • A diet low in sugar, processed starches, and sodas and high in vegetables and fruits decreases risk of cavities
  • Increased whole grains, calcium from dairy products, and exercise may lower risk of periodontal disease

Integrative Interventions

  • Probiotic lozenges: In a clinical study, adults with periodontal disease were treated with either probiotic lozenges providing the S. salivarius strain M18 bacteria or no lozenges. The M18 probiotic group were found to have less plaque, better gum health, and less bleeding on probing than the no-lozenge group.
  • Xylitol: Xylitol has been found to decrease salivary acidity; reduce levels of plaque, harmful bacteria, and inflammation of the gums; and prevent dry mouth and enamel erosion.
  • Coenzyme Q10 (CoQ10): A randomized controlled trial of CoQ10 in patients with periodontal disease who underwent root planing and scaling found a significant reduction in gum inflammation in the CoQ10 group compared with placebo.
  • Fish oil: Findings from several studies suggest people with periodontal disease have lower intake of anti-inflammatory omega-3 fats. Fish oil has been shown to benefit many of the chronic diseases that periodontal disease is associated with (including cardiovascular disease, type 2 diabetes, and autoimmune diseases).
  • Lycopene: Clinical trials in participants with gingivitis or periodontal disease found that lycopene taken orally was more effective than placebo as an adjunct to dental treatment.

2 Introduction

Oral health disorders are among the most common health problems in US adults. Chief among these are dental caries (cavities), caused by tooth decay, and periodontal disease. Periodontal disease encompasses gingivitis (inflammation of the gums) and periodontitis, a potentially aggressive condition that can eventually lead to tooth loss. About 20% of people 65 and older have untreated tooth decay, and approximately half of US adults aged 30 and older have periodontitis (AAP 2015; Kim 2010; Thornton-Evans 2013).

You may be unaware that neglecting oral hygiene harms more than your smile. Poor oral health is linked to heart disease, diabetes, autoimmune diseases, chronic kidney disease, Alzheimer’s disease, and osteoporosis (Hajishengallis 2015; Gulati 2013; Schenkein 2013; Watts 2008; Fisher 2010). Periodontal disease is also associated with a significantly increased risk of death from any cause (Chen 2015; Ricardo 2015). These concerning associations are linked to systemic inflammation, which can be triggered by periodontal disease (Artese 2015; Winning 2015; Craig 2009).

But there is good news. Periodontal disease treatment has been associated with improvements in overall health such as reduced systemic inflammation, endothelial dysfunction, blood pressure, and early atherosclerosis; and some evidence suggests that treatment of periodontal disease may help improve blood sugar control among diabetics (Griffiths 2010; Tonetti 2013; Lockhart 2012; Vergnes 2015; Teeuw 2010). Periodontal treatment has even been proposed as a strategy for reducing the risk of dying from heart disease (Yao 2009).

Given the potentially deadly consequences of poor oral health, preventing periodontal disease should be a major concern for aging individuals. Harmful bacteria in the mouth contribute to plaque buildup and destruction of periodontal tissue (Aruni 2015; Edwards 2010; Mayo Clinic 2014a). Dietary sugars and processed starches feed these bacteria and speed up tooth decay and periodontal disease (Mayo Clinic 2014a). But reducing sugar and processed starch intake and supplementing with an oral probiotic lozenge containing Streptococcus salivarius M18 to displace the bad bacteria in the mouth has been demonstrated to preserve periodontal health (Scariya 2015). Proper at-home dental hygiene, regular dentist visits, and a healthy diet are also essential for preventing periodontal disease (Mayo Clinic 2014a).

In this protocol, you will learn about the many health problems that poor oral health can cause, and how insufficient dental hygiene can promote systemic inflammation and disease. You will read about a unique oral probiotic that fights bad bacteria in the mouth and helps preserve healthy teeth and gums. You will also learn about emerging dental techniques such as laser therapy and photodynamic therapy. This protocol also reviews several integrative interventions that support oral health, such as omega-3 fatty acids and coenzyme Q10 to combat inflammation and support healthy gums.

3 Background

Tooth decay and periodontal disease begin with plaque buildup. Plaque is an oral biofilm composed of microorganisms and a slimy matrix they produce. This biofilm adheres to the teeth and gums (Aruni 2015). Acidic byproducts of bacterial activity cause tooth decay and eventual formation of cavities (Edwards 2010; Mayo Clinic 2014a). An imbalance in the oral microbial community undermines healthy immunity throughout the body and triggers an inflammatory response in the structures that support the teeth. Over the long term, this causes local tissue destruction that can ultimately lead to tooth loss. Systemic inflammation driven by periodontal disease contributes to the link between poor oral health and whole-body health problems (Fernandez-Solari 2015; Hajishengallis 2015; Mayo Clinic 2014b).

According to the American Dental Association, the tooth surface may be considered sound (no decay), or have initial, moderate, or advanced decay (Young 2015). Root cavities are the most common type of dental cavity in older adults. They occur on tooth root surfaces that become exposed when the gums are inflamed or receding (Mayo Clinic 2014a; Bignozzi 2014; Edwards 2010; Gluzman 2013; Ritter 2010).

Periodontal disease is generally classified according to the degree of tissue involvement (Loesche 1996).

  • Gingivitis, which is inflammation affecting primarily the gingiva (gums), is the milder form of periodontal disease. It is usually caused by plaque (Kawar 2011; Page 1986; Peedikayil 2015).
  • Periodontitis is more serious than gingivitis because it affects the gums, periodontal ligament, and bone, can lead to tooth loss, and is associated with systemic diseases (Hajishengallis 2015). It can be chronic, characterized in part by slow to moderate progression, though periods of rapidly progressive tissue destruction may occur; or it can be aggressive, with rapid tissue destruction. In either case, periodontitis may be localized to a specific region of the mouth or may be widespread (Highfield 2009). Periodontitis is also associated with certain diseases (eg, diabetes) and medications (eg, some asthma medications, oral contraceptives) (Kawar 2011; Shashikiran 2007; Heasman 2014).

Large pockets of infection known as abscesses may arise as a result of periodontitis, and may be acute or chronic (Patel 2011). Necrotizing periodontal disease is a particularly severe form in which there may be sudden and rapid destruction of periodontal tissue (Highfield 2009; Herrera 2014).

4 Oral Health and Systemic Diseases

A link between advanced periodontal disease and increased risk of death from all causes was reported in 1998 (Garcia 1998). Since then, the body of research suggesting periodontal disease may be a risk factor for a range of chronic diseases has grown dramatically (Mawardi 2015).

Cardiovascular Disease

Numerous studies show that chronic periodontitis is associated with increased risk of atherosclerosis, stroke, and coronary artery disease (Kholy 2015; Carramolino-Cuellar 2014; Gulati 2013). Fortunately, treating periodontitis can reduce systemic inflammation, improve cardiovascular health, and reduce stroke risk (Piconi 2009; Tonetti 2007; Fisher 2010; Lee 2013; Jeffcoat 2014; Lockhart 2012; Tonetti 2013). For a detailed discussion of strategies to support cardiovascular health, refer to Life Extension’s Atherosclerosis and Cardiovascular Disease protocol.

Type 2 Diabetes

Periodontal disease is one of the many complications of diabetes (Carramolino-Cuellar 2014; Gulati 2013). More severe periodontitis has been observed in individuals with poorly controlled diabetes compared with those whose diabetes is well managed (Lim 2007). Periodontal disease may also adversely affect blood glucose control and risk of diabetic complications (Negrato 2013); and treatment of periodontal disease may improve blood glucose control and hemoglobin A1C (HbA1C) in diabetics (Moeintaghavi 2012; Gulati 2013; Vergnes 2015; Teeuw 2010).

Respiratory Disease

Periodontal disease is associated with chronic obstructive pulmonary disease (COPD) (Usher 2013; Prasanna 2011; Scannapieco 2003; Martos 2011), and more severe periodontal disease is significantly associated with COPD flare-ups (Liu 2012). Some researchers have proposed that bacteria that cause periodontal disease may be inhaled into the lungs, giving rise to respiratory infections and pneumonia (Bansal, Khatri 2013).

Cognitive Decline and Alzheimer’s Disease

Periodontal disease has chronic infectious and inflammatory components, both of which have been associated with Alzheimer’s disease (Kamer 2008; Abbayya 2015; Watts 2008; Wu 2014; Shaik 2014). One study found elevated levels of antibodies to periodontal disease bacteria years before the onset of cognitive decline (Sparks Stein 2012). Tooth loss and poor oral health have been correlated with poor cognitive function (Luo 2015; Saito 2013; Listl 2014). For a more detailed discussion about cognitive function, refer to Life Extension’s Age-Related Cognitive Decline and Alzheimer’s disease protocols.

Chronic Kidney Disease

People with chronic kidney disease are more likely to have periodontal disease, and periodontal disease is associated with declining kidney function and worsening chronic kidney disease. Treatment of periodontal disease has been shown to reduce markers of systemic inflammation in people with chronic kidney disease, especially those undergoing hemodialysis (Chen 2015; Grubbs 2015; Wahid 2013). Those interested in learning more about ways to support healthy kidney function should review the Kidney Health and Chronic Kidney Disease protocols.

Autoimmune Diseases

Periodontal disease is common in people with rheumatoid arthritis. And early evidence suggests treatment of periodontal disease may reduce markers of disease activity in rheumatoid arthritis (Mays 2012; Payne 2015; Kaur, Bright 2014). Similarly, treatment of periodontitis in systemic lupus erythematosus (SLE) patients has been shown to improve measures of SLE disease activity (Fabbri 2014). A more thorough discussion of these conditions can be found in Life Extension’s Rheumatoid Arthritis and Lupus protocols.

Several other autoimmune diseases also appear to be related to periodontal disease: Hashimoto’s thyroiditis (Patil, Patil, Gururaj 2011), Sjögren’s syndrome (Olate 2014), psoriasis (Nakib 2013), and scleroderma (systemic sclerosis) (Baron 2015). Dry mouth, a known contributor to tooth decay and periodontal disease, is a symptom of several autoimmune diseases and may underlie their connection with cavities and periodontal disease (Mays 2012; Mortazavi 2014). On the other hand, systemic inflammation triggered by periodontal disease may contribute to autoimmune diseases (Bansal, Rastogi 2013; Gulati 2013).

Cancer

Certain cancers are more common in people with periodontal disease (Whitmore 2014). These include head and neck (Han 2014; Zeng 2013), pancreatic (Michaud 2013), gastrointestinal, uterine, and prostate cancers (Arora 2010).

Other Conditions

Other conditions that may be associated with periodontal disease include osteoporosis, erectile dysfunction, prostatitis, liver disease, and endometriosis (Gulati 2013; Kavoussi 2009; Hajishengallis 2015; Nagao 2014; Yoneda 2012). Also, periodontal disease has been associated with adverse pregnancy outcomes. Early research suggests treatment of periodontal disease in pregnant women leads to fewer pre-term deliveries and better outcomes (Parihar 2015).

5 Causes and Risk Factors

Causes

Tooth decay and cavities are largely caused by acid secreted by bacteria. This acid erodes the hard enamel on the tooth surface, eventually exposing the vulnerable interior of the tooth (Mayo Clinic 2014a). Dysbiosis is thought to be an important cause of periodontal disease. Dysbiosis occurs when disease-causing bacteria that promote inflammation and break down teeth and gums (and in severe cases, even bone) overcome the normal balance of bacteria in the mouth and in the biofilm (Hajishengallis 2015; Mayo Clinic 2014b; Zaura 2014). Examples of bacteria that can contribute to periodontal disease include Streptococcus sobrinus (S. sobrinus), S. mutans, and some Actinomyces species (Kalesinskas 2014; Fazili 2015; Sutter 1984).

Risk Factors

Caries (cavities). Risk factors for cavities in adults include high dietary sugar, poor dental hygiene, dry mouth, worn fillings, and poorly fitting dental devices. In addition, medical conditions that increase oral exposure to digestive acid, such as gastroesophageal reflux disease and bulimia nervosa, lead to enamel erosion, tooth decay, and cavities. Deeply grooved teeth are more prone to cavities, as are tooth surfaces that are hard to access for cleaning (Mayo Clinic 2014a).

Periodontal disease. Periodontal disease risk is influenced by the composition of the oral microbial community, which can increase or decrease risk. There are several other behavioral, genetic, and environmental risk factors for periodontal disease (Kawar 2011):

  • Smoking tobacco, and possibly marijuana (Thomson 2008; UMMC 2013; Gulati 2013)
  • Older age (especially 65 or older) (Hajishengallis 2014; Kawar 2011)
  • Female gender, especially during hormonal changes such as puberty and pregnancy (Gulati 2013; UMMC 2013)
  • Family history (UMMC 2013)
  • Obesity and metabolic syndrome (Bharti 2009; Kawar 2011)
  • Other systemic diseases, including autoimmune diseases and immune-deficiency diseases like leukemia and AIDS (UMMC 2013)
  • Dental problems related to wisdom teeth or poorly fitting crowns or fillings (UMMC 2013)
  • Stress, anxiety, and depression (UMMC 2013; Oppermann 2012)

6 Signs and Symptoms

Caries (Cavities)

People with tooth decay often do not experience symptoms at first, but as the decay deepens and a cavity forms, they may experience hot and cold sensitivity and tooth pain. Left untreated, a pocket of infection known as an abscess may form, resulting in tooth loss (Mayo Clinic 2014a).

Periodontal Disease

Periodontal disease typically causes minimal symptoms at first. As the condition progresses, signs and symptoms such as gum redness, swelling, sensitivity, and bleeding during brushing and flossing become more likely. A dental practitioner may see gum recession, deepening pockets between teeth and gums, and bleeding on probing during an exam. Halitosis, or bad breath, may be noted. Left untreated, gingival deterioration can progress, and affected teeth can become loose and shift position or be lost (Gurav 2012; Mayo Clinic 2014b; Kawar 2011; UMMC 2013).

7 Diagnosis

History of symptoms such as tooth or gum sensitivity, pain, or bleeding is suggestive of a dental problem and warrants further investigation. During a dental exam, a dental practitioner will look for plaque and tartar buildup, sites of tooth discoloration and softness that indicate decay, gum redness and swelling, gum recession and separation from adjacent teeth, and tooth mobility. A periodontal probe is used to measure pocket depths and check for gum bleeding. X-rays can be used to confirm cavities or assess alveolar bone loss (Mayo Clinic 2014b; Mayo Clinic 2014a; Kawar 2011; Young 2015).

8 Treatment

Caries (Cavities)

Tooth decay in its earliest stage—before the development of cavities—may be treatable with newer methods utilizing specialized dental sealants, resins, or gums, or fluoride liquid or gel applied directly to the teeth by a dental practitioner. These treatments may remineralize enamel that has been eroded by bacterial acids or seal off decayed areas from further exposure to erosive acids (Stahl 2007; Borges 2011). Once cavities have formed, a dentist will need to remove the part of the tooth affected by decay and replace it with a filling or crown. If the infection has reached the pulp at the center of the tooth, a root canal, in which the root pulp is removed and replaced with a special filling, may be performed in an attempt to save the tooth; however, severely decayed teeth sometimes cannot be repaired and need to be extracted. The options for replacing extracted teeth include bridges and implants (Mayo Clinic 2014a).

Periodontal Disease

Gingivitis can frequently be managed with diligent home dental hygiene and regular cleanings performed by a dental practitioner (Kawar 2011). The recommended time between cleanings is based on the severity of the gingivitis and other individual factors (ADA 1997). Toothpastes and mouthwashes that contain antimicrobial substances such as xylitol and essential oils are frequently used to help control plaque (UMMC 2013; Sharma 2010; Vlachojannis 2013).

Treatment of periodontitis can involve several strategies, depending on the severity of disease:

  • Scaling and root planing. These are considered “deep cleaning” procedures. Scaling uses ultrasonic and manual instruments to remove calculus and plaque from tooth surfaces above and below the gum line. Root planing smoothes the root surface so plaque and calculus are less likely to accumulate. The primary purpose of these procedures is to reduce bacterial load in periodontal pockets. Scaling and root planing are generally sufficient treatment for gingivitis and mild periodontitis (Nardi 2012; Paramashivaiah 2013; Singh 2012; Kawar 2011; UMMC 2013).
  • Antibiotics. Antibiotics are sometimes used topically at the site of infection in milder cases, or orally (systemically) in more advanced cases (Kawar 2011). Prescription mouthwashes containing the antimicrobial agent chlorhexidine may be recommended for use before and after periodontal surgery. Side effects of chlorhexidine mouthwashes include temporary tooth discoloration, and rarely, severe allergic reactions (UMMC 2013; Sugano 2012). However, antibiotic use in periodontal disease has come into question since they appear to add little to the efficacy of scaling and root planing and increasing numbers of oral bacteria are becoming resistant to commonly-used antibiotics (Sugano 2012). Doxycycline, a common antibiotic, may be used orally at very low doses to slow destruction of the gums and periodontal ligament (Tariq 2012; Kawar 2011).
  • Surgery. Flap surgery, or periodontal pocket reduction, involves removing sections of the gum that are severely affected, creating access to deeper tissues and the tooth root so cleaning techniques can be more effective. Surgical options for addressing tissue degeneration include gum grafts and bone grafts (UMMC 2013; Kawar 2011).

9 Novel and Emerging Strategies

Diagnostics

Innovative diagnostic technologies have the potential to usher in a new era in the evaluation and management of periodontal disease. Biomolecules found in saliva and in gum crevices can now be measured to gauge inflammation and bone remodeling, and guide more effective screening and treatment. This technology has the potential to allow convenient in-office analysis that can lead to individualized treatment (Taylor 2014; Ram 2015). Tests for additional biomolecules that impact periodontal disease are being investigated; these may allow a sensitive analysis of bacterial, genetic, immunological, and stress-related factors (Patil, Patil 2011). Currently available salivary tests that measure bacterial and human DNA give insight into genetic susceptibility to periodontal disease even before symptoms occur. These tests allow for earlier and more accurate diagnosis and treatment (Nabors 2010). Ongoing research continues to identify unique genetic patterns associated with increased periodontal disease risk (Shaffer 2014).

Interventions

Minimally invasive dentistry. Conventional dental care often involves aggressive mechanical treatment of even minor caries, colloquially termed the “drill and fill” approach. But emerging evidence suggests this aged practice—it has permeated dental dogma for over a century—may be unnecessarily invasive in many cases. Also, dental fillings, or restorations, may deteriorate over time necessitating replacement, which entails additional drilling that further undermines the structural integrity of the tooth (Borges 2011; Stahl 2007).

It turns out that progression of mild caries can often be halted, or even reversed, through the use of remineralizing agents and protective resins and sealants. In these procedures, gentle etching of affected tooth surfaces followed by application of a remineralizing agent and sealant facilitates tooth remineralization and prevents further erosion of tooth enamel. One of the newer widely studied remineralizing agents is casein phosphopeptide-amorphous calcium phosphate, or CPP-ACP (Borges 2011; Stahl 2007).

In the modern era, invasive “drill and fill” dentistry is beginning to fall out of favor, with more preference being given to minimally invasive clinical treatments coupled with at-home use of remineralizing agents such as fluoride- and CPP-ACP-containing mouthwashes and gums along with xylitol, a sugar alcohol that helps displace pathogenic oral bacteria (Emamieh 2015; Borges 2011; Stahl 2007; Milgrom 2006).

Laser. Dental lasers, due to their antibacterial effects and ability to access hard-to-reach sites while minimizing damage to tooth surfaces, can improve the efficacy of traditional periodontal treatments (Zhao 2014). Although one literature review found laser treatment to be as effective as scaling and root planing in improving periodontal health, another review found lasers ineffective for calculus removal, suggesting the role of lasers in conventional treatment of periodontitis requires further investigation (Zhao 2014; Kamath 2014). However, emerging evidence suggests laser treatment plus conventional scaling and root planing may be more effective than scaling and root planing alone (Cheng 2015; Roncati 2014).

Photodynamic therapy. In photodynamic therapy, a special photosensitizing chemical that specifically binds to bacteria is used. A laser, or visible light of a particular wavelength, is then directed at the area to which the photosensitizer has been applied. In the presence of oxygen, the light reacts with the photosensitizer and produces reactive oxygen species that kill bacteria without damaging surrounding tissue (Vohra 2015; Mielczarek-Badora 2013). Antimicrobial photodynamic therapy may help remove biofilm in deep root pockets, increasing the efficiency of scaling and root planing and potentially avoiding post-treatment hypersensitivity (Mielczarek-Badora 2013; Mang 2012). Photodynamic therapy may also be considered as an alternative to antibiotics due to its instantaneous antibacterial effects, reduced likelihood of resistance, absence of toxicity to periodontal tissue, and no known effects in other parts of the body (Vohra 2015). Several reviews have concluded that the addition of antimicrobial photodynamic therapy to conventional scaling and planing more effectively treats periodontal disease compared with scaling and planing alone (Vohra 2015; Smiley 2015; Mielczarek-Badora 2013).

Tissue engineering. Tissue engineering is a technologically advanced method of regenerating or reconstructing healthy periodontal tissue and supporting bone that has been lost to periodontal disease. These innovative techniques may eventually help activate the body’s own restorative self-repair mechanisms, modulating immune activity, promoting new bone growth, and inhibiting loss of existing bone structure. Tissue engineering uses new specialized materials, genetic modification, stem cell therapies, or biomolecules called growth factors (Sood 2012; Rios 2011; Racz 2014). Tissue engineering is a rapidly growing field of research and has great potential to offer a new approach to chronic and aggressive periodontitis treatment; however, only some of these methods have been incorporated into current periodontal treatment (Chen 2010; Sood 2012; Rios 2011).

Medications

Metformin and atorvastatin (Lipitor) are two widely-used medications that treat diabetes and cardiovascular disease, conditions associated with periodontal disease. These drugs have shown promise for their beneficial effects on periodontal health.

Metformin. Metformin is generally considered to be the first-line drug treatment for type 2 diabetes (Rena 2013). But metformin has a remarkably wide range of therapeutic indications beyond diabetes: there is strong evidence that it reduces the risk of multiple types of cancer, improves response to cancer treatment, increases likelihood of survival in some forms of cancer, and mimics some of the anti-aging benefits of caloric restriction (Zhang 2011; Lee 2012; Wang 2014; Zhang 2012; Wang 2013; Yu 2014; Kasznicki 2014; Col 2012; Song 2012; Skinner 2013; Noto 2012; Storozhuk 2013; Anisimov 2013; Stein 2012; Fontana 2004; Pryor 2015). 

Now, emerging evidence indicates metformin’s benefits may extend to periodontal disease as well. In two controlled clinical trials, topical metformin was applied directly to affected periodontal tissues in people being treated for chronic periodontitis with scaling and root planing. After six months of treatment, subjects treated with metformin had reduced periodontal pocket depth, better gingival attachment, and improvements in bony defects compared with those receiving placebo (Pradeep, Rao 2013; Pradeep 2015). Similar results were seen in a trial involving smokers with chronic periodontitis (Rao 2013).

Atorvastatin. Atorvastatin, widely used to treat high cholesterol and reduce cardiovascular risk (AHA 2014), appears to reduce periodontal inflammation as well. In one study, 71 participants with suspected or known atherosclerosis were treated with either 10 or 80 mg per day of atorvastatin. After 12 weeks, those on the higher dose had significantly reduced levels of periodontal inflammation, which was accompanied by an improvement in vascular inflammation (Subramanian 2013). In another trial, 60 subjects with periodontitis were treated with scaling and root planing plus either topical atorvastatin or placebo for nine months; subjects receiving topical atorvastatin had greater reductions in periodontal pocket depths and better gingival attachment compared with placebo (Pradeep, Kumari 2013).

10 Diet and Lifestyle Considerations

Diet

A diet high in sugar and processed starches increases the risk of tooth decay and cavities (Touger-Decker 2003). This is because microbes including Streptococcus mutans (S. mutans) digest dietary carbohydrates and produce acids that erode tooth enamel (Mayo Clinic 2014a; Struzycka 2014). Fresh fruits and vegetables increase saliva flow, which helps wash food particles from teeth (Mayo Clinic 2014a), while eating foods that leave sugar in contact with teeth for long periods of time, such as sticky and gummy sweets, is thought to increase cavity risk (Mayo Clinic 2014a; Palacios 2009). Sugary sodas bathe the teeth in both acid and sugar and are therefore strong promoters of tooth decay (Kaplowitz 2011).

On the other hand, milk and milk products contain proteins that discourage the attachment of cavity-related bacteria to tooth surfaces (Johansson 2011), as well as phosphorus and calcium compounds that appear to promote remineralization of tooth enamel (Kaplowitz 2011; Palacios 2009). Studies have shown increased intake of calcium from dairy may be associated with lower risk of periodontal disease, and low dietary calcium intake is associated with more severe periodontal disease and tooth loss (Kulkarni 2014). In addition, rinsing with water or drinking unsweetened coffee or tea can help remove sugars from tooth surfaces (Mayo Clinic 2014a).

Vegetarians had better periodontal health than non-vegetarians in one controlled clinical trial (Staufenbiel 2013). In another study, men with the highest intake of whole grains had a 23% lower risk of periodontitis compared with men with the lowest whole grain intake (Merchant 2006).

Dental Hygiene

Brushing and flossing effectively remove plaque. Combined with regular dental care, brushing and flossing are critical for preventing cavities and periodontal disease (Struzycka 2014; Mayo Clinic 2014a). Tooth brushing at least twice daily is recommended to prevent tooth decay, with soft toothbrushes that cause less mechanical trauma to gum tissue generally preferred (Carvalho Rde 2007; Zimmer 2010; Mayo Clinic 2014a). Electric toothbrushes have been shown to outperform manual toothbrushes (Stoltze 1994; Hamerlynck 2005). Dental flossing, using either traditional string floss or a water flosser (eg, Waterpik), to clean between teeth is also important (Mayo Clinic 2014a; UMMC 2013). Several studies suggest water flossers, such as those manufactured by Waterpik, are superior to string floss for plaque removal and gum protection (Goyal 2013; Lyle 2012; Magnuson 2013). Home fluoride rinses, anti-bacterial rinses, and professionally applied fluoride treatments can also contribute to cavity prevention (Gluzman 2013; Mayo Clinic 2014a).

Exercise

One study found that lack of physical activity is associated with poor periodontal health and increased risk of periodontal disease, while another large study found that higher levels of physical activity appear to protect against periodontal disease (Bawadi 2011; Merchant 2003). Preclinical and clinical research has shown that exercise reduces gingival oxidative stress and inflammation (Azuma 2011; Mendoza-Nunez 2014), which may contribute to improvements in periodontal health observed in older adults who engage in physical activity (Mendoza-Nunez 2014).

11 Integrative Interventions

Probiotics

Antibiotics and antimicrobials have long been a mainstay of periodontal disease treatment. However, there is a growing recognition that periodontal disease is caused in large part by oral dysbiosis, and the emergence of increasing numbers of antibiotic-resistant bacterial strains may limit the value of antibiotic treatment for periodontal disease. This has led researchers to investigate the potential of probiotics to restore healthy oral flora. Probiotics are microorganisms that, when delivered as a supplement, displace harmful bacteria and deliver health benefits. Probiotic bacteria that can establish long-term colonies in the oral biofilm may be helpful in preventing and treating periodontal disease (Deepa 2009; Woo 2013; Krayer 2010; Scariya 2015; Sugano 2012; Hajishengallis 2015).

One of the most promising of these bacteria is Streptococcus salivarius (S. salivarius) strain M18. In a clinical study, adults with moderate and severe gingivitis and moderate periodontitis were treated with either probiotic lozenges providing the S. salivarius strain M18 bacteria or no lozenges for 30 days (Scariya 2015). They were examined twice during the treatment period, and 15 and 30 days after the end of treatment. Subjects in the probiotic group were found to have less plaque, better gingival health, and less bleeding on probing than the no-probiotic group; specifically:

  • The plaque index score decreased 44% by day 30
  • The gingival index score decreased 42% by day 30
  • The sulcular bleeding index score decreased 53% by day 30
  • The probing pocket depth decreased 20% by day 30

Intriguingly, subjects who received the S. salivarius M18 probiotic lozenges exhibited superior scores on these indices even 30 days after they stopped using the lozenges. This study demonstrated the ability of the probiotic lozenge to significantly improve all four of these commonly used assessments of periodontal health. S. salivarius M18’s ability to colonize the oral cavity contributed to the sustained benefits seen even after the supplementation period ended.

In children, a randomized controlled trial demonstrated supplementation with S. salivarius strain M18 reduced plaque buildup. In addition, salivary bacterial cultures showed children with greater numbers of S. salivarius M18 after treatment also had reduced numbers of cavity-associated S. mutans, which suggests supplementing with this probiotic may prevent cavities (Burton 2013). S. salivarius M18 has also been shown to improve bad breath (halitosis) (Burton 2006).

S. salivarius M18 promotes oral health via several mechanisms. First, it produces enzymes that break down plaque. Next, the probiotic helps maintain healthy oral cavity pH, which is important because imbalanced pH in the mouth can lead to tooth demineralization. Finally, S. salivarius M18 produces powerful antimicrobial compounds called bacteriocin-like inhibitory substances (BLIS) or lantibiotics. These lantibiotics then destroy disease-causing bacteria in the mouth (Burton 2013; Loesche 1996; Heng 2011; Wescombe 2011; Burton 2010).

An article published in Science Advances provides intriguing evidence that Alzheimer’s disease could be caused, in part, by infection with Porphyromonas gingivalis, a keystone pathogen of chronic periodontitis which is a significant risk factor for developing amyloid beta plaques, dementia, and Alzheimer’s.

The scientists studied and compared brain tissue samples from Alzheimer’s disease patients and neurologically normal controls. Interestingly, they found a portion of the “healthy” brains were infected as well, indicating that “…brain infection with P. gingivalis is not a result of poor dental care following the onset of dementia or a consequence of late-stage disease, but is an early event that can explain the pathology found in middle-aged individuals before cognitive decline” (Dominy 2019). These findings suggest better dental care earlier in life may promote brain health later in life.

Xylitol

Xylitol is a small carbohydrate sometimes used in the food industry as a sugarless sweetener. It has been widely studied over the past four decades for its anti-plaque and anti-cavity effects, and has been found to decrease salivary acidity; reduce levels of plaque, harmful bacteria, and gingival inflammation; prevent dry mouth and enamel erosion; and improve salivary flow (Chattopadhyay 2014; NCBI 2015; Nayak 2014). One trial showed xylitol consumption reduced levels of cavity-causing S. mutans bacteria immediately after use, and this effect continued after the subjects stopped using xylitol (Fraga 2010).

Supported by a growing body of evidence demonstrating its beneficial effects, xylitol is now available in therapeutic anti-cavity toothpastes, candies, chewing gums, syrups, and mouthwashes (Lif Holgerson 2006; Nayak 2014; Yuen 2012).

Coenzyme Q10

Evidence for a deficiency of coenzyme Q10 (CoQ10) in gum tissue of patients with periodontal disease, and for a beneficial effect of CoQ10 supplementation in these patients, has existed for decades (Iwamoto 1975; Littarru 1971; Nakamura 1974). The mechanisms behind this relationship lie in CoQ10’s important role in controlling inflammation and regulating oxidative stress (Prakash 2010).

A randomized controlled trial of 120 mg of CoQ10 in 30 patients who underwent root planing and scaling found a significant reduction in inflammation of the gums in the CoQ10 group after one and three months compared with placebo (Manthena 2015). In preclinical and clinical studies using topical oral applications of CoQ10 to diseased periodontal tissue, CoQ10 therapy improved periodontal health and inflammation, including as an adjunct to scaling and root planing (Hanioka 1994; Hans 2012; Sale 2014; Yoneda 2013; Chatterjee, Kandwal 2012). An animal study showed CoQ10 moderated the negative effects of omega-6 fatty acids on periodontal-related bone loss (Varela-Lopez 2015).

Fish Oil

Fish oil and its omega-3 fatty acids, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), have shown benefit in a variety of inflammation-related conditions, including cardiovascular disease, diabetes, and autoimmune diseases (Kremer 1995; Calder 2013; Ellulu 2015; Tabbaa 2013). Interestingly, periodontal disease is bidirectionally associated with these conditions (Koutsochristou 2015; Flemmig 1991; Mays 2012; Ogrendik 2013; Patil, Patil, Gururaj 2011; Mayer 2013; Hollan 2013; Altamash 2015). Findings from several studies suggest people with periodontal disease have lower intake of anti-inflammatory omega-3 fats (Iwasaki 2010; Naqvi 2010) and a relatively greater intake of pro-inflammatory omega-6 fatty acids (Iwasaki 2011; Tabbaa 2013). In one study, 80 patients being treated for periodontitis with scaling and root planing were given either 900 mg EPA plus DHA and 81 mg aspirin daily or placebo. After six months, those receiving the omega-3 supplements and aspirin had more improvement in pocket depths and better gingival health (El-Sharkawy 2010).

Lycopene

Lycopene is a red plant pigment found in foods including tomatoes, watermelon, papaya, and pink grapefruit. Lycopene is in the family of plant compounds known as carotenoids and, like other carotenoids, has well-established anti-inflammatory activity (Gupta 2015). A randomized controlled trial in 20 healthy participants with signs of gingivitis found that 8 mg per day of lycopene taken orally was significantly more effective than placebo as an adjunct to regular dental care in the treatment of gingivitis (Chandra 2007). Similarly, another clinical trial in 42 patients with chronic periodontitis already being treated with scaling and root planing found that 8 mg of lycopene per day resulted in greater improvement in indices of periodontal health compared with placebo (Arora 2013). In a randomized trial, patients with both periodontitis and diabetes were treated with scaling and root planing alone or in combination with 8 mg of lycopene per day. Those taking lycopene had greater reductions in periodontal pocket depths as well as improvements in blood glucose control (Reddy 2015).

Vitamin E

Vitamin E, particularly gamma-tocopherol, may favorably influence periodontal disease, while in animals, alpha-tocopherol has improved gingival healing, prevented bone loss, and decreased local inflammation. Lower blood vitamin E levels have been associated with more severe periodontal disease (Zong 2015). One study found lower blood and saliva levels of superoxide dismutase (SOD), an important enzyme that quenches oxygen free radicals, in 38 subjects with chronic periodontitis compared to 22 people without periodontal disease. The periodontitis subjects were then treated with scaling and root planing alone or with the addition of 200 mg (300 IU) of vitamin E every other day. After three months the vitamin E group had greater improvements in periodontal health. In addition, SOD levels increased in those receiving vitamin E (Singh 2014).

Curcumin

Curcumin, a polyphenolic phytonutrient from the culinary spice turmeric, is a well-known anti-inflammatory agent (Nagpal 2013). It has also shown anti-microbial activity against bacteria implicated in gingivitis and periodontitis (Shahzad 2015). Several studies have demonstrated that curcumin, applied directly to the gums, demonstrates effectiveness comparable to conventional antimicrobials and is a useful adjunct to scaling and root planing for gingivitis and chronic periodontitis (Muglikar 2013; Behal 2011; Jaswal 2014; Anuradha 2015). In laboratory studies, curcumin has inhibited periodontal disease bacteria and biofilm (Izui 2015; Shahzad 2015).

Rodent studies have shown that supplemental curcumin can reduce periodontal disease-related inflammation in the mouth by inhibiting the expression of inflammatory cytokines and reducing activation of the inflammatory mediator nuclear factor-kappaB in gum tissue, resulting in noticeably lower signs of inflammation (Guimaraes 2012; Guimaraes 2011). These studies used the equivalent of 386 ‒ 1287 mg of curcumin per day for a 175 lb person. In a randomized controlled trial, a highly bioavailable form of curcumin called BCM-95 was found to deliver up to seven times more bioactive curcumin to the blood than previous curcumin preparations (Antony 2008).

Lactoferrin

Lactoferrin, an iron-binding protein with anti-microbial and immune-modulating properties, is found in saliva and other body fluids (Berlutti 2011). In the mouth, lactoferrin has been shown to help control the growth of colonies of plaque-related bacteria that contribute to both tooth decay and periodontal disease. It inhibits formation of pathogenic biofilm and can help reduce established biofilm. In a clinical study, treatment with a liposomal lactoferrin tablet providing 180 mg lactoferrin daily in five adults with periodontal disease improved periodontal pocket depths after just four weeks (Ishikado 2010). In another clinical study, oral lactoferrin reduced levels of disease-causing bacteria under the gums of chronic periodontitis patients, favorably influencing the biofilm (Wakabayashi 2010). A preclinical study concluded that orally administered lactoferrin may be a powerful treatment and preventive therapy for periodontal inflammation (Kawazoe 2013), while two other laboratory studies demonstrated that lactoferrin can inhibit the growth and biofilm formation of periodontal disease-associated bacteria (Wakabayashi 2009; Dashper 2012).

Periodontal Tissue Support

Calcium and vitamin D. Calcium and vitamin D deficiencies are associated with osteoporosis, periodontal bone loss, and tooth loss, and adequate intakes are necessary for dental and periodontal health (Miley 2009; Garcia 2011; Stewart 2012). In addition to enhancing calcium uptake and metabolism, vitamin D has anti-inflammatory and immune-modulating properties, both critically important for the maintenance of periodontal health (Stein 2014; Dietrich 2005). Vitamin D also helps prevent other chronic inflammatory conditions including cardiovascular disease and diabetes (Stein 2014).

Supplementation with calcium plus vitamin D may be beneficial for people with periodontal disease. In a preliminary study, subjects who took at least 400 IU vitamin D and 1000 mg calcium daily had less severe periodontal disease compared with subjects who did not take these supplements (Miley 2009). These same subjects were followed for one year, and those who took vitamin D and calcium supplements improved more rapidly, with the greatest difference seen after 6 months of treatment (Garcia 2011). Another study in patients being treated for chronic periodontitis found supplementation with 250 IU vitamin D and 500 mg calcium per day for three months led to markedly better measures of periodontal disease compared with no supplemental calcium and vitamin D (Perayil 2015).

A large study that incorporated findings from a food survey, blood tests, and dental exams concluded that low calcium intake results in more severe periodontal disease (Nishida 2000). In another study, women with the highest calcium intake were 47% less likely to have periodontal disease than women with the lowest intake (Tanaka 2014). Similarly, individuals with low vitamin D status have been found to be more likely to have periodontal disease (Antonoglou 2015; Dietrich 2005), and higher vitamin D intake may protect against periodontal disease progression (Alshouibi 2013).

B vitamin complex. B vitamins are necessary for cell growth and metabolism (Kulkarni 2014). A study in 30 subjects with periodontitis, treated with flap surgery, examined the effects of a vitamin B complex supplement. (In flap surgery, severely infected sections of the gum are removed, creating access to deeper tissues and tooth root.) After surgery, participants received either placebo or a supplement providing 50 mg each of B1 (thiamine), B2 (riboflavin), B3 (niacinamide), B5 (pantothenic acid), and B6 (pyridoxine); 50 mcg each of vitamin B12 (cobalamin) and biotin; and 400 mcg of folic acid per day for 30 days. These subjects were then followed up for 180 days. Those treated with vitamin B complex after surgery had more improvement in gingival attachment at the end of the study (Neiva 2005).

Folate. Folate is critical for normal cell division and tissue repair. It has a special role in maintaining periodontal health, and folate deficiency is linked to oral health problems including infections and degeneration and destruction of the gingiva, periodontal ligament, and alveolar bone (George 2013). Individuals with periodontitis have been found to have lower folate levels compared with those without periodontal disease, and a mouthwash with 5 mg folate per 5 mL (1 tsp) has been shown to improve periodontal health in people with periodontal disease (Pack 1984; Yu 2007).

Smoking depletes folate (Vardavas 2008; Gabriel 2006), which may help explain the co-occurrence of smoking and periodontal disease (George 2013). The association between smoking and folate depletion has led some researchers to recommend folate supplementation for smokers with periodontal disease (Erdemir, Bergstrom 2006; George 2013).

Magnesium. Magnesium is necessary for a wide range of cellular functions. Low magnesium intake has been linked to periodontitis (Staudte 2012). In one study, people with the highest magnesium intake had a 36% lower risk of tooth loss compared to people with the lowest intake (Tanaka 2006), and several studies have observed lower levels of magnesium in the blood of individuals with periodontal disease (Meisel 2005; Pushparani 2014). Smoking and diabetes may worsen the magnesium deficit seen in people with periodontitis (Kolte 2012; Pushparani 2014). Individuals with periodontal disease, and particularly smokers (Erdemir, Erdemir 2006), may fare better if they maintain higher blood magnesium levels.

There is also ample evidence that magnesium deficiency is associated with cardiovascular disease, and is commonly seen in people with other chronic inflammatory conditions including metabolic syndrome and diabetes (Nielsen 2014).

Vitamin C. Vitamin C plays a critical role in connective tissue repair processes and regulation of the immune response throughout the body, making it an important factor in the health of the periodontium (Gokhale 2013). In fact, swelling and bleeding of the gingiva is a hallmark of vitamin C deficiency (Ben-Zvi 2012; Alagl 2015; Rubinoff 1989). Vitamin C may also help maintain alveolar bone and help control the balance of oral bacteria (Alagl 2015).

In a randomized controlled trial, 120 participants were divided into four groups of 30. The first group had no periodontal disease, the second had chronic gingivitis, the third had chronic periodontitis, and the fourth had chronic periodontitis and type 2 diabetes. Subjects with periodontal disease were treated with scaling and root planing, half of whom were randomized to receive 450 mg per day chewable vitamin C or placebo for three weeks. Vitamin C administration resulted in significantly greater reductions in gingival bleeding compared with placebo in the chronic gingivitis and the diabetes plus chronic periodontitis groups (Gokhale 2013).

Zinc. Zinc reduces dental plaque and is effective against bad breath. It also has wound healing, immune-supportive, and antibacterial properties that can all contribute to periodontal health (Kulkarni 2014). In one study, zinc deficiency was associated with an increased number of cavities and poorer gingival health in children (Atasoy 2012). Low zinc levels have also been noted in people with both diabetes and periodontitis (Pushparani 2014).

Additional Support

Green tea. Green tea leaves are a rich source of polyphenols called catechins, which are well known for their ability to reduce oxidative stress and inflammation (Nugala 2012; Babu 2008). Epigallocatechin gallate (EGCG) is the most abundant and most studied of green tea’s catechins (Hamilton-Miller 2001; Anita 2014; Wolfram 2007). Researchers have found that green tea catechins have antibacterial activity against cavity-causing bacteria such as S. mutans and bacteria implicated in periodontal disease such as Porphyromonas gingivalis (Hirasawa 2002). Green tea catechins may also promote oral health by preventing plaque formation (Hamilton-Miller 2001), inhibiting enzymes involved in tissue breakdown (Chatterjee, Saluja 2012; Nugala 2012), and preventing alveolar bone loss (Chatterjee, Saluja 2012; Nugala 2012).

A survey in Japanese men found that green tea intake was associated with better oral health. For each cup of tea consumed per day, there was a measurable benefit observed in the form of decreased average pocket depth, improved gingival attachment, and reduced gingival bleeding (Kushiyama 2009). Drinking green tea has been recommended as a strategy for maintaining periodontal health in patients with periodontitis (Ramasamy 2015).

Green tea catechin extracts have been used as an ingredient in mouthwash or applied directly to tissues with periodontal disease. This method has demonstrated efficacy comparable to conventional antimicrobial mouthwash in reducing plaque, and can enhance the effectiveness of scaling and root planing to treat chronic periodontitis (Kaur, Jain 2014; Kudva 2011; Hattarki 2013; Chava 2013).

Pomegranate. Pomegranates are high in a wide array of beneficial polyphenol phytonutrients demonstrated to prevent cancer, cardiovascular disease, diabetes and other conditions. Pomegranate polyphenols are potent defenders against oxidative stress and inflammation (Basu 2013; Prasad 2014; Jurenka 2008). A mouthwash that contained pomegranate extract, added to scaling and root planing, performed comparably to a conventional antimicrobial chemical, and other localized applications of pomegranate have shown benefit in treatment of periodontal disease (Batista 2014; Sastravaha 2005; DiSilvestro 2009).

Essential oils. Essential oils are aromatic plant extracts rich in compounds called monoterpenes. Mouthwashes and toothpastes with essential oils and monoterpenes from plants such as peppermint and clove have long been in use, and scientists now recognize that the antimicrobial effects of these compounds may explain much of their benefit for oral health (Zomorodian 2015; Allaker 2009). For example, Listerine mouthwashes contain three monoterpenes: menthol, thymol, and eucalyptol (Allaker 2009). Numerous studies have shown that Listerine use is associated with decreased levels of harmful oral bacteria, plaque, and gingival inflammation (Goutham 2013; Charles 2014; Cortelli 2013; Cosyn 2013). A randomized controlled trial in chronic periodontitis patients found that an essential oil mouthwash significantly reduced populations of two types of pathogenic bacteria, and concluded that an essential oil rinse may be an effective adjunct to standard treatment for reducing bacterial counts in gum pockets (Morozumi 2013).

A study involving a mouthwash made with the essential oil from the Ayurvedic herb Ocimum sanctum, also known as holy basil or tulsi (Cohen 2014), found positive periodontal effects (Gupta 2014). In another study, 49 participants with gingivitis were treated with topical 2.5% tea tree oil gel, 0.2% chlorhexidine gel, or placebo gel applied with a toothbrush twice daily for eight weeks. The major monoterpenes in tea tree oil are cineole and terpineol. The greatest improvements in gingival health were seen in the tea tree oil group (Soukoulis 2004).

AAP. American Academy of Periodontology. CDC: Half of American Adults Have Periodontal Disease. https://www.perio.org/consumer/cdc-study.htm. Copyright 2015. Accessed 10/29/2015.

Abbayya K, Puthanakar NY, Naduwinmani S, Chidambar YS. Association between Periodontitis and Alzheimer's Disease. North American journal of medical sciences. Jun 2015;7(6):241-246.

ADA. American Dental Association. Science/Research: Gingival Inflammation Without Loss of Periodontal Attachment (Gingivitis). Available at http://www.ada.org/en/science-research/dental-practice-parameters/gingival-inflammation-without-loss-of-periodontal-attachment. Last updated 1997. Accessed 10/19/2015.

AHA. American Heart Association. Conditions: Drug Therapy for Cholesterol. Available at http://www.heart.org/HEARTORG/Conditions/Cholesterol/PreventionTreatmentofHighCholesterol/Drug-Therapy-for-Cholesterol_UCM_305632_Article.jsp#.ViaXrRCrTeQ. Last updated 04/21/2014. Accessed 10/20/2015.

Alagl AS, Bhat SG. Ascorbic acid: new role of an age-old micronutrient in the management of periodontal disease in older adults. Geriatrics & gerontology international. Mar 2015;15(3):241-254.

Allaker RP, Douglas CW. Novel anti-microbial therapies for dental plaque-related diseases. International journal of antimicrobial agents. Jan 2009;33(1):8-13.

Alshouibi EN, Kaye EK, Cabral HJ, Leone CW, Garcia RI. Vitamin D and periodontal health in older men. Journal of dental research. Aug 2013;92(8):689-693.

Altamash M, Klinge B, Engstrom PE. Periodontal treatment and HbA1c levels in subjects with diabetes mellitus. Journal of oral rehabilitation. Aug 30 2015.

Anisimov VN. Metformin: do we finally have an anti-aging drug? Cell cycle (Georgetown, Tex.). Nov 15 2013;12(22):3483-3489.

Anita P, Sivasamy S, Madan Kumar PD, Balan IN, Ethiraj S. In vitro antibacterial activity of Camellia sinensis extract against cariogenic microorganisms. Journal of basic and clinical pharmacy. Dec 2014;6(1):35-39.

Antonoglou GN, Knuuttila M, Niemela O, Raunio T, Karttunen R, Vainio O, . . . Tervonen T. Low serum level of 1,25(OH)2 D is associated with chronic periodontitis. Journal of periodontal research. Apr 2015;50(2):274-280.

Antony B, Merina B, Iyer VS, Judy N, Lennertz K, Joyal S. A Pilot Cross-Over Study to Evaluate Human Oral Bioavailability of BCM-95CG (Biocurcumax), A Novel Bioenhanced Preparation of Curcumin. Indian journal of pharmaceutical sciences. Jul-Aug 2008;70(4):445-449.

Anuradha BR, Bai YD, Sailaja S, Sudhakar J, Priyanka M, Deepika V. Evaluation of Anti-Inflammatory Effects of Curcumin Gel as an Adjunct to Scaling and Root Planing: A Clinical Study. Journal of international oral health : JIOH. Jul 2015;7(7):90-93.

Arora M, Weuve J, Fall K, Pedersen NL, Mucci LA. An exploration of shared genetic risk factors between periodontal disease and cancers: a prospective co-twin study. American journal of epidemiology. Jan 15 2010;171(2):253-259.

Arora N, Avula H, Avula JK. The adjunctive use of systemic antioxidant therapy (lycopene) in nonsurgical treatment of chronic periodontitis: a short-term evaluation. Quintessence international (Berlin, Germany : 1985). 2013;44(6):395-405.

Artese HP, Foz AM, Rabelo Mde S, Gomes GH, Orlandi M, Suvan J, . . . Romito GA. Periodontal therapy and systemic inflammation in type 2 diabetes mellitus: a meta-analysis. PloS one. 2015;10(5):e0128344.

Aruni AW, Dou Y, Mishra A, Fletcher H. The Biofilm Community: Rebels with a Cause. Curr Oral Health Rep. 2015;2(1):48-56.

Atasoy HB, Ulusoy ZI. The relationship between zinc deficiency and children's oral health. Pediatric dentistry. Sep-Oct 2012;34(5):383-386.

Azuma T, Tomofuji T, Endo Y, Tamaki N, Ekuni D, Irie K, . . . Morita M. Effects of exercise training on gingival oxidative stress in obese rats. Archives of oral biology. Aug 2011;56(8):768-774.

Babu PV, Liu D. Green tea catechins and cardiovascular health: an update. Current medicinal chemistry. 2008;15(18):1840-1850.

Bansal M, Khatri M, Taneja V. Potential role of periodontal infection in respiratory diseases - a review. Journal of medicine and life. Sep 15 2013;6(3):244-248.

Bansal M, Rastogi S, Vineeth NS. Influence of periodontal disease on systemic disease: inversion of a paradigm: a review. Journal of medicine and life. 2013;6(2):126-130.

Baron M, Hudson M, Tatibouet S, Steele R, Lo E, Gravel S, . . . Gornitsky M. Relationship between disease characteristics and orofacial manifestations in systemic sclerosis: Canadian Systemic Sclerosis Oral Health Study III. Arthritis care & research. May 2015;67(5):681-690.

Basu A, Newman ED, Bryant AL, Lyons TJ, Betts NM. Pomegranate polyphenols lower lipid peroxidation in adults with type 2 diabetes but have no effects in healthy volunteers: a pilot study. Journal of nutrition and metabolism. 2013;2013:708381.

Batista AL, Lins RD, de Souza Coelho R, do Nascimento Barbosa D, Moura Belem N, Alves Celestino FJ. Clinical efficacy analysis of the mouth rinsing with pomegranate and chamomile plant extracts in the gingival bleeding reduction. Complementary therapies in clinical practice. Feb 2014;20(1):93-98.

Bawadi HA, Khader YS, Haroun TF, Al-Omari M, Tayyem RF. The association between periodontal disease, physical activity and healthy diet among adults in Jordan. Journal of periodontal research. Feb 2011;46(1):74-81.

Behal R, Mali AM, Gilda SS, Paradkar AR. Evaluation of local drug-delivery system containing 2% whole turmeric gel used as an adjunct to scaling and root planing in chronic periodontitis: A clinical and microbiological study. Journal of Indian Society of Periodontology. Jan 2011;15(1):35-38.

Ben-Zvi GT, Tidman MJ. Be vigilant for scurvy in high-risk groups. The Practitioner. Oct 2012;256(1755):23-25, 23.

Berlutti F, Pilloni A, Pietropaoli M, Polimeni A, Valenti P. Lactoferrin and oral diseases: current status and perspective in periodontitis. Annali di stomatologia. Mar 2011;2(3-4):10-18.

Bharti V, Khurana P. Metabolic syndrome and periodontal disease. Journal of Indian Society of Periodontology. Sep 2009;13(3):172-174.

Bignozzi I, Crea A, Capri D, Littarru C, Lajolo C, Tatakis DN. Root caries: a periodontal perspective. Journal of periodontal research. Apr 2014;49(2):143-163.

Borges BC, de Souza Borges J, de Araujo LS, Machado CT, Dos Santos AJ, de Assuncao Pinheiro IV. Update on nonsurgical, ultraconservative approaches to treat effectively non-cavitated caries lesions in permanent teeth. European journal of dentistry. Apr 2011;5(2):229-236.

Burton J, Chilcott C, Wescombe P, et al. Extended Safety Data for the Oral Cavity Probiotic Streptococcus Salivarius K12. Probiotics & Antimicro. Prot. 2010;2:135-144.

Burton JP, Chilcott CN, Moore CJ, Speiser G, Tagg JR. A preliminary study of the effect of probiotic Streptococcus salivarius K12 on oral malodour parameters. J Appl Microbiol. Apr 2006;100(4):754-764.

Burton JP, Drummond BK, Chilcott CN, Tagg JR, Thomson WM, Hale JD, Wescombe PA. Influence of the probiotic Streptococcus salivarius strain M18 on indices of dental health in children: a randomized double-blind, placebo-controlled trial. J Med Microbiol. Jun 2013;62(Pt 6):875-884.

Calder PC. Omega-3 polyunsaturated fatty acids and inflammatory processes: nutrition or pharmacology? British journal of clinical pharmacology. Mar 2013;75(3):645-662.

Carramolino-Cuellar E, Tomas I, Jimenez-Soriano Y. Relationship between the oral cavity and cardiovascular diseases and metabolic syndrome. Medicina oral, patologia oral y cirugia bucal. May 2014;19(3):e289-294.

Carvalho Rde S, Rossi V, Weidlich P, Oppermann RV. Comparative analysis between hard- and soft-filament toothbrushes related to plaque removal and gingival abrasion. The Journal of clinical dentistry. 2007;18(3):61-64.

Chandra RV, Prabhuji ML, Roopa DA, Ravirajan S, Kishore HC. Efficacy of lycopene in the treatment of gingivitis: a randomised, placebo-controlled clinical trial. Oral health & preventive dentistry. 2007;5(4):327-336.

Charles CA, Lisante TA, Revankar R, Cortelli JR, Cortelli SC, Aquino D, . . . Amini P. Early benefits with daily rinsing on gingival health improvements with an essential oil mouthrinse--post-hoc analysis of 5 clinical trials. Journal of dental hygiene : JDH / American Dental Hygienists' Association. 2014;88 Suppl 1:40-50.

Chatterjee A, Kandwal A, Singh N, Singh A. Evaluation of Co-Q10 anti-gingivitis effect on plaque induced gingivitis: A randomized controlled clinical trial. J Indian Soc Periodontol. Oct 2012;16(4):539-542.

Chatterjee A, Saluja M, Agarwal G, Alam M. Green tea: A boon for periodontal and general health. J Indian Soc Periodontol. Apr 2012;16(2):161-167.

Chattopadhyay S, Raychaudhuri U, Chakraborty R. Artificial sweeteners - a review. Journal of food science and technology. Apr 2014;51(4):611-621.

Chava VK, Vedula BD. Thermo-reversible green tea catechin gel for local application in chronic periodontitis: a 4-week clinical trial. Journal of periodontology. Sep 2013;84(9):1290-1296.

Chen FM, Jin Y. Periodontal tissue engineering and regeneration: current approaches and expanding opportunities. Tissue engineering. Part B, Reviews. Apr 2010;16(2):219-255.

Chen YT, Shih CJ, Ou SM, Hung SC, Lin CH, Tarng DC. Periodontal Disease and Risks of Kidney Function Decline and Mortality in Older People: A Community-Based Cohort Study. American journal of kidney diseases : the official journal of the National Kidney Foundation. Aug 2015;66(2):223-230.

Cheng Y, Chen JW, Ge MK, Zhou ZY, Yin X, Zou SJ. Efficacy of adjunctive laser in non-surgical periodontal treatment: a systematic review and meta-analysis. Lasers in medical science. Sep 2 2015.

Cohen MM. Tulsi - Ocimum sanctum: A herb for all reasons. Journal of Ayurveda and integrative medicine. Oct-Dec 2014;5(4):251-259.

Col NF, Ochs L, Springmann V, Aragaki AK, Chlebowski RT. Metformin and breast cancer risk: a meta-analysis and critical literature review. Breast cancer research and treatment. Oct 2012;135(3):639-646.

Cortelli SC, Cortelli JR, Shang H, McGuire JA, Charles CA. Long-term management of plaque and gingivitis using an alcohol-free essential oil containing mouthrinse: a 6-month randomized clinical trial. American journal of dentistry. Jun 2013;26(3):149-155.

Cosyn J, Princen K, Miremadi R, Decat E, Vaneechoutte M, De Bruyn H. A double-blind randomized placebo-controlled study on the clinical and microbial effects of an essential oil mouth rinse used by patients in supportive periodontal care. International journal of dental hygiene. Feb 2013;11(1):53-61.

Craig RG. Destructive periodontal diseases, systemic inflammation, and atherosclerotic complications: the emerging role of the dental profession. Journal of the California Dental Association. Nov 2009;37(11):773-777.

Dashper SG, Pan Y, Veith PD, Chen YY, Toh EC, Liu SW, . . . Reynolds EC. Lactoferrin inhibits Porphyromonas gingivalis proteinases and has sustained biofilm inhibitory activity. Antimicrob Agents Chemother. Mar 2012;56(3):1548-1556.

Deepa D, Mehta DS. Is the role of probiotics friendly in the treatment of periodontal diseases !! Journal of Indian Society of Periodontology. Jan 2009;13(1):30-31.

Dietrich T, Nunn M, Dawson-Hughes B, Bischoff-Ferrari HA. Association between serum concentrations of 25-hydroxyvitamin D and gingival inflammation. The American journal of clinical nutrition. Sep 2005;82(3):575-580.

DiSilvestro RA, DiSilvestro DJ, DiSilvestro DJ. Pomegranate extract mouth rinsing effects on saliva measures relevant to gingivitis risk. Phytotherapy research : PTR. Aug 2009;23(8):1123-1127.

Dominy S, Lynch C, Ermini F et al. Porphyromonas gingivalis in Alzheimer’s disease brains: Evidence for disease causation and treatment with small-molecule inhibitors. Sci Adv. 2019;5(1):eaau3333.

Edwards PC, Kanjirath P. Recognition and Management of Common Acute Conditions of the Oral Cavity Resulting From Tooth Decay, Periodontal Disease, and Trauma: An Update for the Family Physician. The Journal of the American Board of Family Medicine. 2010;23(3):285-294.

El-Sharkawy H, Aboelsaad N, Eliwa M, Darweesh M, Alshahat M, Kantarci A, . . . Van Dyke TE. Adjunctive treatment of chronic periodontitis with daily dietary supplementation with omega-3 Fatty acids and low-dose aspirin. Journal of periodontology. Nov 2010;81(11):1635-1643.

Ellulu MS, Khaza'ai H, Abed Y, Rahmat A, Ismail P, Ranneh Y. Role of fish oil in human health and possible mechanism to reduce the inflammation. Inflammopharmacol. Jun 2015;23(2-3):79-89.

Emamieh S, Khaterizadeh Y, Goudarzi H, Ghasemi A, Baghban AA, Torabzadeh H. The effect of two types chewing gum containing casein phosphopeptide-amorphous calcium phosphate and xylitol on salivary Streptococcus mutans. Journal of conservative dentistry : JCD. May-Jun 2015;18(3):192-195.

Erdemir EO, Bergstrom J. Relationship between smoking and folic acid, vitamin B12 and some haematological variables in patients with chronic periodontal disease. J Clin Periodontol. Dec 2006;33(12):878-884.

Erdemir EO, Erdemir A. The detection of salivary minerals in smokers and non-smokers with chronic periodontitis by the inductively coupled plasma-atomic emission spectrophotometry technique. Journal of periodontology. Jun 2006;77(6):990-995.

Fabbri C, Fuller R, Bonfa E, Guedes LK, D'Alleva PS, Borba EF. Periodontitis treatment improves systemic lupus erythematosus response to immunosuppressive therapy. Clinical rheumatology. Apr 2014;33(4):505-509.

Fazili T. Antimicrobe. Actinomyces species (Actinomycoses). Monograph. http://www.antimicrobe.org/b73.asp#t13. Accessed 12/4/2015.

Fernandez-Solari J, Barrionuevo P, Mastronardi CA. Periodontal Disease and Its Systemic Associated Diseases. Mediators of inflammation. 2015;2015.

Fisher MA, Borgnakke WS, Taylor GW. Periodontal disease as a risk marker in coronary heart disease and chronic kidney disease. Current opinion in nephrology and hypertension. Nov 2010;19(6):519-526.

Flemmig TF, Shanahan F, Miyasaki KT. Prevalence and severity of periodontal disease in patients with inflammatory bowel disease. Journal of clinical periodontology. Oct 1991;18(9):690-697.

Fontana L, Meyer TE, Klein S, Holloszy JO. Long-term calorie restriction is highly effective in reducing the risk for atherosclerosis in humans. Proceedings of the National Academy of Sciences of the United States of America. Apr 27 2004;101(17):6659-6663.

Fraga CP, Mayer MP, Rodrigues CR. Use of chewing gum containing 15% of xylitol and reduction in mutans streptococci salivary levels. Brazilian oral research. Apr-Jun 2010;24(2):142-146.

Gabriel HE, Crott JW, Ghandour H, Dallal GE, Choi S-W, Keyes MK, . . . Mason JB. Chronic cigarette smoking is associated with diminished folate status, altered folate form distribution, and increased genetic damage in the buccal mucosa of healthy adults. The American journal of clinical nutrition. 2006;83(4):835-841.

Garcia MN, Hildebolt CF, Miley DD, Dixon DA, Couture RA, Spearie CL, . . . Civitelli R. One-year effects of vitamin D and calcium supplementation on chronic periodontitis. Journal of periodontology. Jan 2011;82(1):25-32.

Garcia RI, Krall EA, Vokonas PS. Periodontal disease and mortality from all causes in the VA Dental Longitudinal Study. Ann Periodontol. Jul 1998;3(1):339-349.

George JP, Shobha R, Lazarus FJ. Folic Acid: A positive influence on periodontal tissues during health and disease. Int J Health Allied Sci. 2013;2(3):145-152.

Gluzman R, Katz RV, Frey BJ, McGowan R. Prevention of root caries: a literature review of primary and secondary preventive agents. Special care in dentistry : official publication of the American Association of Hospital Dentists, the Academy of Dentistry for the Handicapped, and the American Society for Geriatric Dentistry. May-Jun 2013;33(3):133-140.

Gokhale NH, Acharya AB, Patil VS, Trivedi DJ, Thakur SL. A short-term evaluation of the relationship between plasma ascorbic acid levels and periodontal disease in systemically healthy and type 2 diabetes mellitus subjects. Journal of dietary supplements. Jun 2013;10(2):93-104.

Goutham BS, Manchanda K, Sarkar AD, Prakash R, Jha K, Mohammed S. Efficacy of two commercially available Oral Rinses - Chlorohexidine and Listrine on Plaque and Gingivitis - A Comparative Study. Journal of international oral health : JIOH. Aug 2013;5(4):56-61.

Goyal CR, Lyle DM, Qaqish JG, Schuller R. Evaluation of the plaque removal efficacy of a water flosser compared to string floss in adults after a single use. The Journal of clinical dentistry. 2013;24(2):37-42.

Griffiths R, Barbour S. Lipoproteins and lipoprotein metabolism in periodontal disease. Clinical lipidology. Jun 2010;5(3):397-411.

Grubbs V, Vittinghoff E, Beck JD, Kshirsagar AV, Wang W, Griswold ME, . . . Young B. Association Between Periodontal Disease and Kidney Function Decline in African Americans: The Jackson Heart Study. Journal of periodontology. Oct 2015;86(10):1126-1132.

Guimaraes MR, Coimbra LS, de Aquino SG, Spolidorio LC, Kirkwood KL, Rossa C, Jr. Potent anti-inflammatory effects of systemically administered curcumin modulate periodontal disease in vivo. Journal of periodontal research. Apr 2011;46(2):269-279.

Guimaraes MR, de Aquino SG, Coimbra LS, Spolidorio LC, Kirkwood KL, Rossa C, Jr. Curcumin modulates the immune response associated with LPS-induced periodontal disease in rats. Innate immunity. Feb 2012;18(1):155-163.

Gulati M, Anand V, Jain N, Anand B, Bahuguna R, Govila V, Rastogi P. Essentials of periodontal medicine in preventive medicine. International journal of preventive medicine. Sep 2013;4(9):988-994.

Gupta D, Bhaskar DJ, Gupta RK, Karim B, Jain A, Singh R, Karim W. A randomized controlled clinical trial of Ocimum sanctum and chlorhexidine mouthwash on dental plaque and gingival inflammation. Journal of Ayurveda and integrative medicine. Apr 2014;5(2):109-116.

Gupta S, Jawanda MK, Arora V, Mehta N, Yadav V. Role of Lycopene in Preventing Oral Diseases as a Nonsurgical Aid of Treatment. International journal of preventive medicine. 2015;6:70.

Gurav AN. Periodontitis and insulin resistance: casual or causal relationship? Diabetes & metabolism journal. Dec 2012;36(6):404-411.

Hajishengallis G. Aging and its Impact on Innate Immunity and Inflammation: Implications for Periodontitis. Journal of oral biosciences / JAOB, Japanese Association for Oral Biology. Feb 1 2014;56(1):30-37.

Hajishengallis G. Periodontitis: from microbial immune subversion to systemic inflammation. Nature reviews. Immunology. Jan 2015;15(1):30-44.

Hamerlynck JV, Middeldorp S, Scholten RJ. [From the Cochrane Library: brushing the teeth with an electric toothbrush with an oscllating rotating movement more effective against plaque and gingivitis than brushing with a conventional toothbrush]. Nederlands tijdschrift voor geneeskunde. Nov 26 2005;149(48):2673-2675.

Hamilton-Miller JM. Anti-cariogenic properties of tea (Camellia sinensis). J Med Microbiol. Apr 2001;50(4):299-302.

Han YW, Houcken W, Loos BG, Schenkein HA, Tezal M. Periodontal disease, atherosclerosis, adverse pregnancy outcomes, and head-and-neck cancer. Advances in dental research. May 2014;26(1):47-55.

Hanioka T, Tanaka M, Ojima M, Shizukuishi S, Folkers K. Effect of topical application of coenzyme Q10 on adult periodontitis. Molecular aspects of medicine. 1994;15 Suppl:s241-248.

Hans M, Prakash S, Gupta S. Clinical evaluation of topical application of perio-Q gel (Coenzyme Q(10)) in chronic periodontitis patients. J Indian Soc Periodontol. Apr 2012;16(2):193-199.

Hattarki SA, Pushpa SP, Bhat K. Evaluation of the efficacy of green tea catechins as an adjunct to scaling and root planing in the management of chronic periodontitis using PCR analysis: A clinical and microbiological study. J Indian Soc Periodontol. Mar 2013;17(2):204-209.

Heasman PA, Hughes FJ. Drugs, medications and periodontal disease. British dental journal. Oct 2014;217(8):411-419.

Heng NC, Haji-Ishak NS, Kalyan A, Wong AY, Lovric M, Bridson JM, . . . Tagg JR. Genome sequence of the bacteriocin-producing oral probiotic Streptococcus salivarius strain M18. J Bacteriol. Nov 2011;193(22):6402-6403.

Herrera D, Alonso B, de Arriba L, Santa Cruz I, Serrano C, Sanz M. Acute periodontal lesions. Periodontology 2000. Jun 2014;65(1):149-177.

Highfield J. Diagnosis and classification of periodontal disease. Australian dental journal. Sep 2009;54 Suppl 1:S11-26.

Hirasawa M, Takada K, Makimura M, Otake S. Improvement of periodontal status by green tea catechin using a local delivery system: a clinical pilot study. Journal of periodontal research. Dec 2002;37(6):433-438.

Hollan I, Meroni PL, Ahearn JM, Cohen Tervaert JW, Curran S, Goodyear CS, . . . Wasko MC. Cardiovascular disease in autoimmune rheumatic diseases. Autoimmunity reviews. Aug 2013;12(10):1004-1015.

Ishikado A, Uesaki S, Suido H, Nomura Y, Sumikawa K, Maeda M, . . . Makino T. Human trial of liposomal lactoferrin supplementation for periodontal disease. Biological & pharmaceutical bulletin. 2010;33(10):1758-1762.

Iwamoto Y, Nakamura R, Folkers K, Morrison RF. Study of periodontal disease and coenzyme Q. Research communications in chemical pathology and pharmacology. Jun 1975;11(2):265-271.

Iwasaki M, Taylor GW, Moynihan P, Yoshihara A, Muramatsu K, Watanabe R, Miyazaki H. Dietary ratio of n-6 to n-3 polyunsaturated fatty acids and periodontal disease in community-based older Japanese: a 3-year follow-up study. Prostaglandins Leukot Essent Fatty Acids. Aug 2011;85(2):107-112.

Iwasaki M, Yoshihara A, Moynihan P, Watanabe R, Taylor GW, Miyazaki H. Longitudinal relationship between dietary omega-3 fatty acids and periodontal disease. Nutrition (Burbank, Los Angeles County, Calif.). Nov-Dec 2010;26(11-12):1105-1109.

Izui S, Sekine S, Maeda K, Kuboniwa M, Takada A, Amano A, Nagata H. Antibacterial Activity of Curcumin Against Periodontopathic Bacteria. Journal of periodontology. Oct 8 2015:1-18.

Jaswal R, Dhawan S, Grover V, Malhotra R. Comparative evaluation of single application of 2% whole turmeric gel versus 1% chlorhexidine gel in chronic periodontitis patients: A pilot study. Journal of Indian Society of Periodontology. Sep 2014;18(5):575-580.

Jeffcoat MK, Jeffcoat RL, Gladowski PA, Bramson JB, Blum JJ. Impact of periodontal therapy on general health: evidence from insurance data for five systemic conditions. American journal of preventive medicine. 2014;47(2):166.

Johansson I, Lif Holgerson P. Milk and oral health. Nestle Nutrition workshop series. Paediatric programme. 2011;67:55-66.

Jurenka JS. Therapeutic applications of pomegranate (Punica granatum L.): a review. Alternative medicine review : a journal of clinical therapeutic. Jun 2008;13(2):128-144.

Kalesinskas P, Kacergius T, Ambrozaitis A, Peciuliene V, Ericson D. Reducing dental plaque formation and caries development. A review of current methods and implications for novel pharmaceuticals. Stomatologija / issued by public institution "Odontologijos studija" ... [et al.]. 2014;16(2):44-52.

Kamath DG, Umesh Nayak S. Detection, removal and prevention of calculus: Literature Review. The Saudi dental journal. Jan 2014;26(1):7-13.

Kamer AR, Craig RG, Dasanayake AP, Brys M, Glodzik-Sobanska L, de Leon MJ. Inflammation and Alzheimer's disease: possible role of periodontal diseases. Alzheimers Dement. Jul 2008;4(4):242-250.

Kaplowitz GJ. An update on the dangers of soda pop. Dental assistant (Chicago, Ill. : 1994). Jul-Aug 2011;80(4):14-16, 18-20, 22-13 passim; quiz 29-31.

Kasznicki J, Sliwinska A, Drzewoski J. Metformin in cancer prevention and therapy. Annals of translational medicine. Jun 2014;2(6):57.

Kaur H, Jain S, Kaur A. Comparative evaluation of the antiplaque effectiveness of green tea catechin mouthwash with chlorhexidine gluconate. J Indian Soc Periodontol. Mar 2014;18(2):178-182.

Kaur S, Bright R, Proudman SM, Bartold PM. Does periodontal treatment influence clinical and biochemical measures for rheumatoid arthritis? A systematic review and meta-analysis. Seminars in arthritis and rheumatism. Oct 2014;44(2):113-122.

Kavoussi SK, West BT, Taylor GW, Lebovic DI. Periodontal disease and endometriosis: analysis of the National Health and Nutrition Examination Survey. Fertility and sterility. Feb 2009;91(2):335-342.

Kawar N, Gajendrareddy PK, Hart TC, Nouneh R, Maniar N, Alrayyes S. Periodontal disease for the primary care physician. Disease-a-month : DM. Apr 2011;57(4):174-183.

Kawazoe A, Inubushi T, Miyauchi M, Ishikado A, Tanaka E, Tanne K, Takata T. Orally administered liposomal lactoferrin inhibits inflammation-related bone breakdown without interrupting orthodontic tooth movement. Journal of periodontology. Oct 2013;84(10):1454-1462.

Kholy KE, Genco RJ, Van Dyke TE. Oral infections and cardiovascular disease. Trends in endocrinology and metabolism: TEM. Jun 2015;26(6):315-321.

Kim SH, Seo BM, Choung PH, Lee YM. Adult stem cell therapy for periodontal disease. International journal of stem cells. May 2010;3(1):16-21.

Kolte AP, Kolte RA, Laddha RK. Effect of smoking on salivary composition and periodontal status. J Indian Soc Periodontol. Jul 2012;16(3):350-353.

Koutsochristou V, Zellos A, Dimakou K, Panayotou I, Siahanidou S, Roma-Giannikou E, Tsami A. Dental Caries and Periodontal Disease in Children and Adolescents with Inflammatory Bowel Disease: A Case-Control Study. Inflammatory bowel diseases. Aug 2015;21(8):1839-1846.

Krayer JW, Leite RS, Kirkwood KL. Non-surgical chemotherapeutic treatment strategies for the management of periodontal diseases. Dental clinics of North America. Jan 2010;54(1):13-33.

Kremer JM, Lawrence DA, Petrillo GF, Litts LL, Mullaly PM, Rynes RI, . . . et al. Effects of high-dose fish oil on rheumatoid arthritis after stopping nonsteroidal antiinflammatory drugs. Clinical and immune correlates. Arthritis and rheumatism. Aug 1995;38(8):1107-1114.

Kudva P, Tabasum ST, Shekhawat NK. Effect of green tea catechin, a local drug delivery system as an adjunct to scaling and root planing in chronic periodontitis patients: A clinicomicrobiological study. J Indian Soc Periodontol. Jan 2011;15(1):39-45.

Kulkarni V, Bhatavadekar NB, Uttamani JR. The effect of nutrition on periodontal disease: a systematic review. Journal of the California Dental Association. May 2014;42(5):302-311.

Kushiyama M, Shimazaki Y, Murakami M, Yamashita Y. Relationship between intake of green tea and periodontal disease. Journal of periodontology. Mar 2009;80(3):372-377.

Lee JH, Jeon SM, Hong SP, Cheon JH, Kim TI, Kim WH. Metformin use is associated with a decreased incidence of colorectal adenomas in diabetic patients with previous colorectal cancer. Dig Liver Dis. Dec 2012;44(12):1042-1047.

Lee YL, Hu HY, Huang N, Hwang DK, Chou P, Chu D. Dental prophylaxis and periodontal treatment are protective factors to ischemic stroke. Stroke; a journal of cerebral circulation. Apr 2013;44(4):1026-1030.

Lif Holgerson P, Stecksen-Blicks C, Sjostrom I, Oberg M, Twetman S. Xylitol concentration in saliva and dental plaque after use of various xylitol-containing products. Caries research. 2006;40(5):393-397.

Lim LP, Tay FB, Sum CF, Thai AC. Relationship between markers of metabolic control and inflammation on severity of periodontal disease in patients with diabetes mellitus. J Clin Periodontol. Feb 2007;34(2):118-123.

Listl S. Oral health conditions and cognitive functioning in middle and later adulthood. BMC oral health. 2014;14:70.

Littarru GP, Nakamura R, Ho L, Folkers K, Kuzell WC. Deficiency of coenzyme Q 10 in gingival tissue from patients with periodontal disease. Proceedings of the National Academy of Sciences of the United States of America. Oct 1971;68(10):2332-2335.

Liu Z, Zhang W, Zhang J, Zhou X, Zhang L, Song Y, Wang Z. Oral hygiene, periodontal health and chronic obstructive pulmonary disease exacerbations. J Clin Periodontol. Jan 2012;39(1):45-52.

Lockhart PB, Bolger AF, Papapanou PN, Osinbowale O, Trevisan M, Levison ME, . . . Baddour LM. Periodontal disease and atherosclerotic vascular disease: does the evidence support an independent association?: a scientific statement from the American Heart Association. Circulation. May 22 2012;125(20):2520-2544.

Loesche WJ. Microbiology of Dental Decay and Periodontal Disease. In: Medical Microbiology. 4th ed. Chapter 99. Galveston (TX): University of Texas Medical Branch at Galveston; 1996. http://www.ncbi.nlm.nih.gov/books/NBK8259.

Luo J, Wu B, Zhao Q, Guo Q, Meng H, Yu L, . . . Ding D. Association between tooth loss and cognitive function among 3063 Chinese older adults: a community-based study. PloS one. 2015;10(3):e0120986.

Lyle DM. Relevance of the water flosser: 50 years of data. Compendium of continuing education in dentistry (Jamesburg, N.J. : 1995). Apr 2012;33(4):278-280, 282.

Magnuson B, Harsono M, Stark PC, Lyle D, Kugel G, Perry R. Comparison of the effect of two interdental cleaning devices around implants on the reduction of bleeding: a 30-day randomized clinical trial. Compendium of continuing education in dentistry (Jamesburg, N.J. : 1995). Nov-Dec 2013;34 Spec No 8:2-7.

Mang TS, Tayal DP, Baier R. Photodynamic therapy as an alternative treatment for disinfection of bacteria in oral biofilms. Lasers in surgery and medicine. Sep 2012;44(7):588-596.

Manthena S, Rao MV, Penubolu LP, Putcha M, Harsha AV. Effectiveness of CoQ10 Oral Supplements as an Adjunct to Scaling and Root Planing in Improving Periodontal Health. Journal of clinical and diagnostic research : JCDR. Aug 2015;9(8):Zc26-28.

Martos R, Marton I. [Possible correlations between periodontitis and chronic obstructive pulmonary disease. Review of the literature]. Fogorvosi szemle. Sep 2011;104(3):87-92.

Mawardi HH, Elbadawi LS, Sonis ST. Current understanding of the relationship between periodontal and systemic diseases. Saudi medical journal. 2015;36(2):150-158.

Mayer Y, Elimelech R, Balbir-Gurman A, Braun-Moscovici Y, Machtei EE. Periodontal condition of patients with autoimmune diseases and the effect of anti-tumor necrosis factor-alpha therapy. Journal of periodontology. Feb 2013;84(2):136-142.

Mayo Clinic. Mayo Clinic. Diseases and Conditions: Cavities/Tooth Decay. Available at http://www.mayoclinic.org/diseases-conditions/cavities/basics/causes/con-20030076?p=1. Last updated 05/30/2014a. Accessed 09/08/2015.

Mayo Clinic. Mayo Clinic. Diseases and Conditions: Periodontitis. Available at http://www.mayoclinic.org/diseases-conditions/periodontitis/basics/causes/con-20021679?p=1. Last updated 02/04/2014b. Accessed 09/08/2015.

Mays JW, Sarmadi M, Moutsopoulos NM. Oral manifestations of systemic autoimmune and inflammatory diseases: diagnosis and clinical management. The journal of evidence-based dental practice. Sep 2012;12(3 Suppl):265-282.

Meisel P, Schwahn C, Luedemann J, John U, Kroemer HK, Kocher T. Magnesium deficiency is associated with periodontal disease. Journal of dental research. Oct 2005;84(10):937-941.

Mendoza-Nunez VM, Hernandez-Monjaraz B, Santiago-Osorio E, Betancourt-Rule JM, Ruiz-Ramos M. Tai Chi exercise increases SOD activity and total antioxidant status in saliva and is linked to an improvement of periodontal disease in the elderly. Oxidative medicine and cellular longevity. 2014;2014:603853.

Merchant AT, Pitiphat W, Franz M, Joshipura KJ. Whole-grain and fiber intakes and periodontitis risk in men. The American journal of clinical nutrition. Jun 2006;83(6):1395-1400.

Merchant AT, Pitiphat W, Rimm EB, Joshipura K. Increased physical activity decreases periodontitis risk in men. European journal of epidemiology. 2003;18(9):891-898.

Michaud DS, Izard J, Wilhelm-Benartzi CS, You DH, Grote VA, Tjonneland A, . . . Riboli E. Plasma antibodies to oral bacteria and risk of pancreatic cancer in a large European prospective cohort study. Gut. Dec 2013;62(12):1764-1770.

Mielczarek-Badora E, Szulc M. Photodynamic therapy and its role in periodontitis treatment. Postepy higieny i medycyny doswiadczalnej (Online). 2013;67:1058-1065.

Miley DD, Garcia MN, Hildebolt CF, Shannon WD, Couture RA, Anderson Spearie CL, . . . Civitelli R. Cross-sectional study of vitamin D and calcium supplementation effects on chronic periodontitis. Journal of periodontology. Sep 2009;80(9):1433-1439.

Milgrom P, Ly KA, Roberts MC, Rothen M, Mueller G, Yamaguchi DK. Mutans streptococci dose response to xylitol chewing gum. Journal of dental research. Feb 2006;85(2):177-181.

Moeintaghavi A, Arab HR, Bozorgnia Y, Kianoush K, Alizadeh M. Non-surgical periodontal therapy affects metabolic control in diabetics: a randomized controlled clinical trial. Australian dental journal. Mar 2012;57(1):31-37.

Morozumi T, Kubota T, Abe D, Shimizu T, Nohno K, Yoshie H. Microbiological effect of essential oils in combination with subgingival ultrasonic instrumentation and mouth rinsing in chronic periodontitis patients. International journal of dentistry. 2013;2013:146479.

Mortazavi H, Baharvand M, Movahhedian A, Mohammadi M, Khodadoustan A. Xerostomia due to systemic disease: a review of 20 conditions and mechanisms. Annals of medical and health sciences research. Jul 2014;4(4):503-510.

Muglikar S, Patil KC, Shivswami S, Hegde R. Efficacy of curcumin in the treatment of chronic gingivitis: a pilot study. Oral health & preventive dentistry. 2013;11(1):81-86.

Nabors TW, McGlennen RC, Thompson D. Salivary testing for periodontal disease diagnosis and treatment. Dentistry today. Jun 2010;29(6):53-54, 56, 58-60; quiz 61.

Nagao Y, Kawahigashi Y, Sata M. Association of Periodontal Diseases and Liver Fibrosis in Patients With HCV and/or HBV infection. Hepatitis Monthly. 2014;14(12):e23264.

Nagpal M, Sood S. Role of curcumin in systemic and oral health: An overview. Journal of natural science, biology, and medicine. Jan 2013;4(1):3-7.

Nakamura R, Littarru GP, Folkers K, Wilkinson EG. Study of CoQ10-enzymes in gingiva from patients with periodontal disease and evidence for a deficiency of coenzyme Q10. Proceedings of the National Academy of Sciences of the United States of America. Apr 1974;71(4):1456-1460.

Nakib S, Han J, Li T, Joshipura K, Qureshi AA. Periodontal disease and risk of psoriasis among nurses in the United States. Acta odontologica Scandinavica. Nov 2013;71(6):1423-1429.

Naqvi AZ, Buettner C, Phillips RS, Davis RB, Mukamal KJ. n-3 fatty acids and periodontitis in US adults. Journal of the American Dietetic Association. Nov 2010;110(11):1669-1675.

Nardi GM, Di Giorgio R, Sabatini S. Effectiveness of tips for delicate micro-ultrasonic root planing comparing to tips for traditional ultrasonic root planing. Annali di stomatologia. Jul 2012;3(3-4):90-94.

Nayak PA, Nayak UA, Khandelwal V. The effect of xylitol on dental caries and oral flora. Clinical, cosmetic and investigational dentistry. 2014;6:89-94.

NCBI. National Center for Biotechnology Information. U. S. National Library of Medicine. Pubchem: Open Chemistry Database. Compound Summary: Xylitol. http://pubchem.ncbi.nlm.nih.gov/compound/xylitol#section=Top. Last updated 11/21/2015. Accessed 11/23/2015.

Negrato CA, Tarzia O, Jovanovic L, Chinellato LE. Periodontal disease and diabetes mellitus. Journal of applied oral science : revista FOB. Jan-Feb 2013;21(1):1-12.

Neiva RF, Al-Shammari K, Nociti FH, Jr., Soehren S, Wang HL. Effects of vitamin-B complex supplementation on periodontal wound healing. Journal of periodontology. Jul 2005;76(7):1084-1091.

Nielsen FH. Effects of magnesium depletion on inflammation in chronic disease. Current opinion in clinical nutrition and metabolic care. Nov 2014;17(6):525-530.

Nishida M, Grossi SG, Dunford RG, Ho AW, Trevisan M, Genco RJ. Calcium and the risk for periodontal disease. Journal of periodontology. Jul 2000;71(7):1057-1066.

Noto H, Goto A, Tsujimoto T, Noda M. Cancer risk in diabetic patients treated with metformin: a systematic review and meta-analysis. PloS one. 2012;7(3):e33411.

Nugala B, Namasi A, Emmadi P, Krishna PM. Role of green tea as an antioxidant in periodontal disease: The Asian paradox. J Indian Soc Periodontol. Jul 2012;16(3):313-316.

Ogrendik M. Rheumatoid arthritis is an autoimmune disease caused by periodontal pathogens. International journal of general medicine. 2013;2013:383-386.

Olate S, Munoz D, Neumann S, Pozzer L, Cavalieri-Pereira L, de Moraes M. A descriptive study of the oral status in subjects with Sjogren's syndrome. International journal of clinical and experimental medicine. 2014;7(4):1140-1144.

Oppermann RV, Weidlich P, Musskopf ML. Periodontal disease and systemic complications. Brazilian oral research. 2012;26 Suppl 1:39-47.

Pack AR. Folate mouthwash: effects on established gingivitis in periodontal patients. J Clin Periodontol. Oct 1984;11(9):619-628.

Page RC. Gingivitis. Journal of clinical periodontology. May 1986;13(5):345-359.

Palacios C, Joshipura K, Willett W. Nutrition and health: guidelines for dental practitioners. Oral diseases. Sep 2009;15(6):369-381.

Paramashivaiah R, Prabhuji ML. Mechanized scaling with ultrasonics: Perils and proactive measures. Journal of Indian Society of Periodontology. Jul 2013;17(4):423-428.

Parihar AS, Katoch V, Rajguru SA, Rajpoot N, Singh P, Wakhle S. Periodontal Disease: A Possible Risk-Factor for Adverse Pregnancy Outcome. Journal of international oral health : JIOH. Jul 2015;7(7):137-142.

Patel PV, KUMAR S, Patel A. Periodontal abscess: a review. Journal of clinical and diagnostic research. 2011;5(2):404-409.

Patil BS, Patil S, Gururaj TR. Probable autoimmune causal relationship between periodontitis and Hashimotos thyroidits: a systemic review. Nigerian journal of clinical practice. Jul-Sep 2011;14(3):253-261.

Patil PB, Patil BR. Saliva: A diagnostic biomarker of periodontal diseases. J Indian Soc Periodontol. Oct-Dec 2011;15(4):310-317.

Payne JB, Golub LM, Thiele GM, Mikuls TR. The Link Between Periodontitis and Rheumatoid Arthritis: A Periodontist's Perspective. Curr Oral Health Rep. 2015;2:20-29.

Peedikayil FC, Sreenivasan P, Narayanan A. Effect of coconut oil in plaque related gingivitis - A preliminary report. Nigerian medical journal : journal of the Nigeria Medical Association. Mar-Apr 2015;56(2):143-147.

Perayil J, Menon KS, Kurup S, Thomas AE, Fenol A, Vyloppillil R, . . . Megha S. Influence of Vitamin D & Calcium Supplementation in the Management of Periodontitis. Journal of clinical and diagnostic research : JCDR. Jun 2015;9(6):Zc35-38.

Piconi S, Trabattoni D, Luraghi C, Perilli E, Borelli M, Pacei M, . . . Clerici M. Treatment of periodontal disease results in improvements in endothelial dysfunction and reduction of the carotid intima-media thickness. FASEB journal : official publication of the Federation of American Societies for Experimental Biology. Apr 2009;23(4):1196-1204.

Pradeep AR, Kumari M, Rao NS, Martande SS, Naik SB. Clinical efficacy of subgingivally delivered 1.2% atorvastatin in chronic periodontitis: a randomized controlled clinical trial. Journal of periodontology. Jul 2013;84(7):871-879.

Pradeep AR, Patnaik K, Nagpal K, Karvekar S, Ramamurthy BL, Naik SB, . . . Raju A. Efficacy of locally-delivered 1% metformin gel in the treatment of intrabony defects in patients with chronic periodontitis: a randomized, controlled clinical trial. Journal of investigative and clinical dentistry. Mar 18 2015.

Pradeep AR, Rao NS, Naik SB, Kumari M. Efficacy of varying concentrations of subgingivally delivered metformin in the treatment of chronic periodontitis: a randomized controlled clinical trial. Journal of periodontology. Feb 2013;84(2):212-220.

Prakash S, Sunitha J, Hans M. Role of coenzyme Q(10) as an antioxidant and bioenergizer in periodontal diseases. Indian journal of pharmacology. Dec 2010;42(6):334-337.

Prasad D, Kunnaiah R. Punica granatum: A review on its potential role in treating periodontal disease. J Indian Soc Periodontol. Jul 2014;18(4):428-432.

Prasanna SJ. Causal relationship between periodontitis and chronic obstructive pulmonary disease. J Indian Soc Periodontol. Oct 2011;15(4):359-365.

Pryor R, Cabreiro F. Repurposing metformin: an old drug with new tricks in its binding pockets. The Biochemical journal. Nov 1 2015;471(3):307-322.

Pushparani DS, Anandan SN, Theagarayan P. Serum zinc and magnesium concentrations in type 2 diabetes mellitus with periodontitis. J Indian Soc Periodontol. Mar 2014;18(2):187-193.

Racz GZ, Kadar K, Foldes A, Kallo K, Perczel-Kovach K, Keremi B, . . . Varga G. Immunomodulatory and potential therapeutic role of mesenchymal stem cells in periodontitis. Journal of physiology and pharmacology : an official journal of the Polish Physiological Society. Jun 2014;65(3):327-339.

Ram VS, Parthiban, Sudhakar U, Mithradas N, Prabhakar R. Bonebiomarkers in periodontal disease: a review article. Journal of clinical and diagnostic research : JCDR. Jan 2015;9(1):Ze07-10.

Ramasamy C. "Potential natural antioxidants: adjuvant effect of green tea polyphenols in periodontal infections". Infectious disorders drug targets. Aug 31 2015.

Rao NS, Pradeep AR, Kumari M, Naik SB. Locally delivered 1% metformin gel in the treatment of smokers with chronic periodontitis: a randomized controlled clinical trial. Journal of periodontology. Aug 2013;84(8):1165-1171.

Reddy PV, Ambati M, Koduganti R. Systemic lycopene as an adjunct to scaling and root planing in chronic periodontitis patients with type 2 diabetes mellitus. Journal of International Society of Preventive & Community Dentistry. May 2015;5(Suppl 1):S25-31.

Rena G, Pearson ER, Sakamoto K. Molecular mechanism of action of metformin: old or new insights? Diabetologia. 2013;56(9):1898-1906.

Ricardo AC, Athavale A, Chen J, Hampole H, Garside D, Marucha P, Lash JP. Periodontal disease, chronic kidney disease and mortality: results from the third National Health and Nutrition Examination Survey. BMC nephrology. 2015;16:97.

Rios HF, Lin Z, Oh B, Park CH, Giannobile WV. Cell- and gene-based therapeutic strategies for periodontal regenerative medicine. Journal of periodontology. Sep 2011;82(9):1223-1237.

Ritter AV, Shugars DA, Bader JD. Root caries risk indicators: a systematic review of risk models. Community dentistry and oral epidemiology. Oct 2010;38(5):383-397.

Roncati M, Gariffo A. Systematic review of the adjunctive use of diode and Nd:YAG lasers for nonsurgical periodontal instrumentation. Photomedicine and laser surgery. Apr 2014;32(4):186-197.

Rubinoff AB, Latner PA, Pasut LA. Vitamin C and oral health. Journal (Canadian Dental Association). Sep 1989;55(9):705-707.

Saito Y, Sugawara N, Yasui-Furukori N, Takahashi I, Nakaji S, Kimura H. Cognitive function and number of teeth in a community-dwelling population in Japan. Annals of general psychiatry. 2013;12(1):20.

Sale ST, Parvez H, Yeltiwar RK, Vivekanandan G, Pundir AJ, Jain P. A comparative evaluation of topical and intrasulcular application of coenzyme Q10 (Perio Q) gel in chronic periodontitis patients: A clinical study. J Indian Soc Periodontol. Jul 2014;18(4):461-465.

Sastravaha G, Gassmann G, Sangtherapitikul P, Grimm WD. Adjunctive periodontal treatment with Centella asiatica and Punica granatum extracts in supportive periodontal therapy. Journal of the International Academy of Periodontology. Jul 2005;7(3):70-79.

Scannapieco FA, Bush RB, Paju S. Associations between periodontal disease and risk for nosocomial bacterial pneumonia and chronic obstructive pulmonary disease. A systematic review. Ann Periodontol. Dec 2003;8(1):54-69.

Scariya L. Probiotics in Periodontal Therapy. Int J Pharm Bio Sci. 2015;6(1):242-50.

Schenkein HA, Loos BG. Inflammatory mechanisms linking periodontal diseases to cardiovascular diseases. Journal of clinical periodontology. 2013;40(s14):S51-S69.

Shaffer JR, Polk DE, Wang X, Feingold E, Weeks DE, Lee MK, . . . Marazita ML. Genome-wide association study of periodontal health measured by probing depth in adults ages 18-49 years. G3 (Bethesda, Md.). Feb 2014;4(2):307-314.

Shahzad M, Millhouse E, Culshaw S, Edwards CA, Ramage G, Combet E. Selected dietary (poly)phenols inhibit periodontal pathogen growth and biofilm formation. Food Funct. Mar 2015;6(3):719-729.

Shaik MM, Ahmad S, Gan SH, Abuzenadah AM, Ahmad E, Tabrez S, . . . Kamal MA. How do periodontal infections affect the onset and progression of Alzheimer's disease? CNS Neurol Disord Drug Targets. Apr 2014;13(3):460-466.

Sharma NC, Araujo MW, Wu MM, Qaqish J, Charles CH. Superiority of an essential oil mouthrinse when compared with a 0.05% cetylpyridinium chloride containing mouthrinse: a six-month study. International dental journal. Jun 2010;60(3):175-180.

Shashikiran ND, Reddy VV, Raju PK. Effect of antiasthmatic medication on dental disease: dental caries and periodontal disease. Journal of the Indian Society of Pedodontics and Preventive Dentistry. Apr-Jun 2007;25(2):65-68.

Singh N, Chander Narula S, Kumar Sharma R, Tewari S, Kumar Sehgal P. Vitamin E supplementation, superoxide dismutase status, and outcome of scaling and root planing in patients with chronic periodontitis: a randomized clinical trial. Journal of periodontology. Feb 2014;85(2):242-249.

Singh S, Uppoor A, Nayak D. A comparative evaluation of the efficacy of manual, magnetostrictive and piezoelectric ultrasonic instruments--an in vitro profilometric and SEM study. Journal of applied oral science : revista FOB. Feb 2012;20(1):21-26.

Skinner HD, Crane CH, Garrett CR, Eng C, Chang GJ, Skibber JM, . . . Das P. Metformin use and improved response to therapy in rectal cancer. Cancer medicine. Feb 2013;2(1):99-107.

Smiley CJ, Tracy SL, Abt E, Michalowicz BS, John MT, Gunsolley J, . . . Hanson N. Systematic review and meta-analysis on the nonsurgical treatment of chronic periodontitis by means of scaling and root planing with or without adjuncts. Journal of the American Dental Association (1939). Jul 2015;146(7):508-524.e505.

Song CW, Lee H, Dings RP, Williams B, Powers J, Santos TD, . . . Park HJ. Metformin kills and radiosensitizes cancer cells and preferentially kills cancer stem cells. Scientific reports. 2012;2:362.

Sood S, Gupta S, Mahendra A. Gene therapy with growth factors for periodontal tissue engineering--a review. Medicina oral, patologia oral y cirugia bucal. Mar 2012;17(2):e301-310.

Soukoulis S, Hirsch R. The effects of a tea tree oil-containing gel on plaque and chronic gingivitis. Australian dental journal. Jun 2004;49(2):78-83.

Sparks Stein P, Steffen MJ, Smith C, Jicha G, Ebersole JL, Abner E, Dawson D, 3rd. Serum antibodies to periodontal pathogens are a risk factor for Alzheimer's disease. Alzheimers Dement. May 2012;8(3):196-203.

Stahl J, Zandona AF. Rationale and protocol for the treatment of non-cavitated smooth surface carious lesions. General dentistry. Mar-Apr 2007;55(2):105-111.

Staudte H, Kranz S, Volpel A, Schutze J, Sigusch BW. Comparison of nutrient intake between patients with periodontitis and healthy subjects. Quintessence international (Berlin, Germany : 1985). Nov-Dec 2012;43(10):907-916.

Staufenbiel I, Weinspach K, Forster G, Geurtsen W, Gunay H. Periodontal conditions in vegetarians: a clinical study. European journal of clinical nutrition. Aug 2013;67(8):836-840.

Stein PK, Soare A, Meyer TE, Cangemi R, Holloszy JO, Fontana L. Caloric restriction may reverse age-related autonomic decline in humans. Aging Cell. Aug 2012;11(4):644-650.

Stein SH, Livada R, Tipton DA. Re-evaluating the role of vitamin D in the periodontium. Journal of periodontal research. Oct 2014;49(5):545-553.

Stewart S, Hanning R. Building osteoporosis prevention into dental practice. Journal (Canadian Dental Association). 2012;78:c29.

Stoltze K, Bay L. Comparison of a manual and a new electric toothbrush for controlling plaque and gingivitis. J Clin Periodontol. Feb 1994;21(2):86-90.

Storozhuk Y, Hopmans SN, Sanli T, Barron C, Tsiani E, Cutz JC, . . . Tsakiridis T. Metformin inhibits growth and enhances radiation response of non-small cell lung cancer (NSCLC) through ATM and AMPK. British journal of cancer. May 28 2013;108(10):2021-2032.

Struzycka I. The oral microbiome in dental caries. Polish journal of microbiology / Polskie Towarzystwo Mikrobiologow = The Polish Society of Microbiologists. 2014;63(2):127-135.

Subramanian S, Emami H, Vucic E, Singh P, Vijayakumar J, Fifer KM, . . . Tawakol A. High-dose atorvastatin reduces periodontal inflammation: a novel pleiotropic effect of statins. Journal of the American College of Cardiology. Dec 24 2013;62(25):2382-2391.

Sugano N. Biological plaque control: novel therapeutic approach to periodontal disease. Journal of oral science. Mar 2012;54(1):1-5.

Sutter VL. Anaerobes as normal oral flora. Reviews of infectious diseases. Mar-Apr 1984;6 Suppl 1:S62-66.

Tabbaa M, Golubic M, Roizen MF, Bernstein AM. Docosahexaenoic acid, inflammation, and bacterial dysbiosis in relation to periodontal disease, inflammatory bowel disease, and the metabolic syndrome. Nutrients. Aug 2013;5(8):3299-3310.

Tanaka K, Miyake Y, Okubo H, Hanioka T, Sasaki S, Miyatake N, Arakawa M. Calcium intake is associated with decreased prevalence of periodontal disease in young Japanese women. Nutrition journal. 2014;13:109.

Tanaka K, Miyake Y, Sasaki S, Ohya Y, Miyamoto S, Matsunaga I, . . . Oda H. Magnesium intake is inversely associated with the prevalence of tooth loss in Japanese pregnant women: the Osaka Maternal and Child Health Study. Magnesium research : official organ of the International Society for the Development of Research on Magnesium. Dec 2006;19(4):268-275.

Tariq M, Iqbal Z, Ali J, Baboota S, Talegaonkar S, Ahmad Z, Sahni JK. Treatment modalities and evaluation models for periodontitis. International journal of pharmaceutical investigation. Jul 2012;2(3):106-122.

Taylor JJ. Protein biomarkers of periodontitis in saliva. ISRN inflammation. 2014;2014:593151.

Teeuw WJ, Gerdes VEA, Loos BG. Effect of Periodontal Treatment on Glycemic Control of Diabetic Patients: A systematic review and meta-analysis. Diabetes care. 2010;33(2):421-427.

Thomson W, Poulton R, Broadbent JM, et al. CAnnabis smoking and periodontal disease among young adults. JAMA : the journal of the American Medical Association. 2008;299(5):525-531.

Thornton-Evans G, Eke P, Wei L, Palmer A, Moeti R, Hutchins S, Borrell LN. Periodontitis among adults aged >/=30 years - United States, 2009-2010. Morbidity and mortality weekly report. Surveillance summaries (Washington, D.C. : 2002). Nov 22 2013;62 Suppl 3:129-135.

Tonetti MS, D'Aiuto F, Nibali L, Donald A, Storry C, Parkar M, . . . Deanfield J. Treatment of periodontitis and endothelial function. The New England journal of medicine. Mar 1 2007;356(9):911-920.

Tonetti MS, Van Dyke TE. Periodontitis and atherosclerotic cardiovascular disease: consensus report of the Joint EFP/AAP Workshop on Periodontitis and Systemic Diseases. Journal of periodontology. Apr 2013;84(4 Suppl):S24-29.

Touger-Decker R, van Loveren C. Sugars and dental caries. The American journal of clinical nutrition. October 1, 2003 2003;78(4):881S-892S.

UMMC. University of Maryland Medical Center. Medical Reference Guide: Periodontal Disease. Available at http://umm.edu/health/medical/reports/articles/periodontal-disease. Last updated 03/11/2013. Accessed 09/08/2015.

Usher AK, Stockley RA. The link between chronic periodontitis and COPD: a common role for the neutrophil? BMC medicine. 2013;11:241.

Vardavas CI, Linardakis MK, Hatzis CM, Malliaraki N, Saris WH, Kafatos AG. Smoking status in relation to serum folate and dietary vitamin intake. Tobacco induced diseases. 2008;4:8.

Varela-Lopez A, Bullon P, Battino M, Ramirez-Tortosa M, Ochoa JJ, Cordero MD, . . . Quiles JL. Coenzyme Q Protects Against Age-Related Alveolar Bone Loss Associated to n-6 Polyunsaturated Fatty Acid Rich-Diets by Modulating Mitochondrial Mechanisms. The journals of gerontology. Series A, Biological sciences and medical sciences. Jul 28 2015.

Vergnes JN. Review finds periodontal treatment has short term benefits for diabetics. Evidence-based dentistry. Sep 2015;16(3):78-79.

Vlachojannis C, Winsauer H, Chrubasik S. Effectiveness and safety of a mouthwash containing essential oil ingredients. Phytotherapy research : PTR. May 2013;27(5):685-691.

Vohra F, Akram Z, Safii SH, Vaithilingam RD, Ghanem A, Sergis K, Javed F. Role of antimicrobial photodynamic therapy in the treatment of aggressive periodontitis: A systematic review. Photodiagnosis and photodynamic therapy. 2015.

Wahid A, Chaudhry S, Ehsan A, Butt S, Ali Khan A. Bidirectional Relationship between Chronic Kidney Disease & Periodontal Disease. Pakistan journal of medical sciences. 2013;29(1):211.

Wakabayashi H, Kondo I, Kobayashi T, Yamauchi K, Toida T, Iwatsuki K, Yoshie H. Periodontitis, periodontopathic bacteria and lactoferrin. Biometals : an international journal on the role of metal ions in biology, biochemistry, and medicine. Jun 2010;23(3):419-424.

Wakabayashi H, Yamauchi K, Kobayashi T, Yaeshima T, Iwatsuki K, Yoshie H. Inhibitory effects of lactoferrin on growth and biofilm formation of Porphyromonas gingivalis and Prevotella intermedia. Antimicrob Agents Chemother. Aug 2009;53(8):3308-3316.

Wang L, Song Y, Wu GN, Yuan DM. Association of the metformin with the risk of lung cancer: a meta-analysis. Transl Lung Cancer Res. Aug 2013;2(4):259-263.

Wang Z, Lai ST, Xie L, Zhao JD, Ma NY, Zhu J, . . . Jiang GL. Metformin is associated with reduced risk of pancreatic cancer in patients with type 2 diabetes mellitus: a systematic review and meta-analysis. Diabetes research and clinical practice. Oct 2014;106(1):19-26.

Watts A, Crimmins EM, Gatz M. Inflammation as a potential mediator for the association between periodontal disease and Alzheimer's disease. Neuropsychiatr Dis Treat. Oct 2008;4(5):865-876.

Wescombe PA, Upton M, Renault P, Wirawan RE, Power D, Burton JP, . . . Tagg JR. Salivaricin 9, a new lantibiotic produced by Streptococcus salivarius. Microbiology. May 2011;157(Pt 5):1290-1299.

Whitmore SE, Lamont RJ. Oral bacteria and cancer. PLoS pathogens. Mar 2014;10(3):e1003933.

Winning L, Patterson CC, Cullen KM, Stevenson KA, Lundy FT, Kee F, Linden GJ. The association between subgingival periodontal pathogens and systemic inflammation. J Clin Periodontol. Sep 2015;42(9):799-806.

Wolfram S. Effects of green tea and EGCG on cardiovascular and metabolic health. Journal of the American College of Nutrition. Aug 2007;26(4):373s-388s.

Woo J, Ahn J. Probiotic-mediated competition, exclusion and displacement in biofilm formation by food-borne pathogens. Letters in applied microbiology. Apr 2013;56(4):307-313.

Wu Z, Nakanishi H. Connection between periodontitis and Alzheimer's disease: possible roles of microglia and leptomeningeal cells. Journal of pharmacological sciences. 2014;126(1):8-13.

Yao Z, Yang J, Pan L, Chen Z. Periodontal treatment: potential to reduce cardiovascular morbidity and/or mortality. Medical hypotheses. Jul 2009;73(1):33-35.

Yoneda M, Naka S, Nakano K, Wada K, Endo H, Mawatari H, . . . Nakajima A. Involvement of a periodontal pathogen, Porphyromonas gingivalis on the pathogenesis of non-alcoholic fatty liver disease. BMC gastroenterology. 2012;12:16.

Yoneda T, Tomofuji T, Ekuni D, Azuma T, Endo Y, Kasuyama K, . . . Morita M. Anti-aging effects of co-enzyme Q10 on periodontal tissues. Journal of dental research. Aug 2013;92(8):735-739.

Young DA, Nový BB, Zeller GG, Hale R, Hart TC, Truelove EL, . . . Beltran-Aguilar E. The American Dental Association Caries Classification System for Clinical Practice. The Journal of the American Dental Association. 2015;146(2):79-86.

Yu H, Yin L, Jiang X, Sun X, Wu J, Tian H, . . . He X. Effect of metformin on cancer risk and treatment outcome of prostate cancer: a meta-analysis of epidemiological observational studies. PloS one. 2014;9(12):e116327.

Yu YH, Kuo HK, Lai YL. The association between serum folate levels and periodontal disease in older adults: data from the National Health and Nutrition Examination Survey 2001/02. Journal of the American Geriatrics Society. Jan 2007;55(1):108-113.

Yuen HK, Westwater C, Degarmo J, Bandyopadhyay D. Immediate Effect of Xylitol Chewing Gum and Mouth Rinse on Salivary Levels of Mutans Streptococci in Adults with Systemic Sclerosis: A Pilot Study. Journal of experimental and integrative medicine. Jan 1 2012;2(1):89-92.

Zaura E, Nicu EA, Krom BP, Keijser BJ. Acquiring and maintaining a normal oral microbiome: current perspective. Frontiers in cellular and infection microbiology. 2014;4:85.

Zeng XT, Deng AP, Li C, Xia LY, Niu YM, Leng WD. Periodontal disease and risk of head and neck cancer: a meta-analysis of observational studies. PloS one. 2013;8(10):e79017.

Zhang ZJ, Zheng ZJ, Kan H, Song Y, Cui W, Zhao G, Kip KE. Reduced risk of colorectal cancer with metformin therapy in patients with type 2 diabetes: a meta-analysis. Diabetes care. Oct 2011;34(10):2323-2328.

Zhang ZJ, Zheng ZJ, Shi R, Su Q, Jiang Q, Kip KE. Metformin for liver cancer prevention in patients with type 2 diabetes: a systematic review and meta-analysis. The Journal of clinical endocrinology and metabolism. Jul 2012;97(7):2347-2353.

Zhao Y, Yin Y, Tao L, Nie P, Tang Y, Zhu M. Er:YAG laser versus scaling and root planing as alternative or adjuvant for chronic periodontitis treatment: a systematic review. J Clin Periodontol. Nov 2014;41(11):1069-1079.

Zimmer S, Öztürk M, Barthel CR, Bizhang M, Jordan RA. Cleaning Efficacy and Soft Tissue Trauma After Use of Manual Toothbrushes With Different Bristle Stiffness. Journal of periodontology. 2010;82(2):267-271.

Zomorodian K, Ghadiri P, Saharkhiz MJ, Moein MR, Mehriar P, Bahrani F, . . . Fani MM. Antimicrobial activity of seven essential oils from Iranian aromatic plants against common causes of oral infections. Jundishapur journal of microbiology. Feb 2015;8(2):e17766.

Zong G, Scott AE, Griffiths HR, Zock PL, Dietrich T, Newson RS. Serum alpha-Tocopherol Has a Nonlinear Inverse Association with Periodontitis among US Adults. The Journal of nutrition. May 2015;145(5):893-899.